Brain Blogger » Neuroscience & Neurology http://brainblogger.com Health and Science Blog Covering Brain Topics Wed, 29 Jul 2015 15:00:33 +0000 en-US hourly 1 http://wordpress.org/?v=4.2.3 Novel Breakthroughs in Parkinson’s Disease Treatment http://brainblogger.com/2015/07/29/novel-breakthroughs-in-parkinsons-disease-treatment/ http://brainblogger.com/2015/07/29/novel-breakthroughs-in-parkinsons-disease-treatment/#comments Wed, 29 Jul 2015 15:00:33 +0000 http://brainblogger.com/?p=20207 Around 7 million people around the world are diagnosed with Parkinson’s disease every year. This is a progressively degenerative disease that has no cure. There have been, however, a number of very encouraging findings published in the last few weeks, some of which are briefly reviewed in this article.

Drugs to manage the symptoms of Parkinson’s disease are available, but they become ineffective after the patient has taken them for a few years. Deep brain stimulation (DBS) is a surgical procedure for patients in the advanced stages of the disease. It involves implanting electrodes in the movement regions of the brain. The electrodes are connected to a pulse generator that is placed under the collarbone and sends electrical signals to the brain. This method can manage symptoms of the disease which include slowness of movement, stiffness, and tremors. But it is expensive, not everyone is deemed fit to go through this 10-15 hour invasive surgical procedure, and the method is believed to trigger cognitive and mood disorders.

The quest was always on to find non-invasive ways to manage the symptoms of Parkinson’s disease. Now there seems to be light at the end of the tunnel. Scientists have discovered that certain drugs and a headband that delivers electrical signals can be used to manage the symptoms of Parkinson’s disease.

Non-invasive brain stimulation

Students at Johns Hopkins University have suggested using a non-invasive therapy called transcranial direct current stimulation (tDCS). In this method, a headband-type device with two electrodes — a cathode and an anode — is fitted over the head of the patient to deliver low-intensity current to specific motor areas of the brain. The current stimulates (under the anode) and inhibits (under the cathode) neurons that, in turn, may control the symptoms of the disease. The device has not yet been tested on humans, but the idea is promising because it is based on sound logic backed by science.

Cortical dysfunctionality has been implicated in Parkinson’s disease. Neuroimaging and neurophysiologic studies have shown that hyper- or hypo-stimulation of certain areas in the brain, like the motor cortices, may trigger symptoms of the disease.

Scientists had recognized the efficacy and safety of non-invasive neuromodulation procedures like tDCS as alternatives to the DBS method quite some time ago. The application of this procedure on subjects with Parkinson’s disease during clinical trials has led to symptomatic relief for short durations, just a few minutes. There were no adverse reactions because the electrodes were placed precisely over those cortical regions that are involved with movement. There were also no unintended outcomes across multiple cortices that are associated with other symptoms.

Scientists believe that stimulating the motor and prefrontal cortices may relieve some symptoms of the disease. Later studies also confirmed that tDCS can improve hand motor functionality in stroke patients. However, all the studies confirm that the primary challenge is to make the benefits of tDCS last longer. The scientists think that repetitive sessions of tDCS using higher-intensity currents can prolong cortical excitability. The stimulation parameters — the strength of the current, the number to be applied per session, the number of sessions and the interval between them, and the specific areas of the brain to be targeted — have to be nailed down precisely to replicate positive results and make predictions. Investigations are underway.

Anti-malarial drugs to fight Parkinson’s disease

The gold standard of current treatment for Parkinson’s disease is dopamine replacement therapy. But this treatment method has its drawbacks, the greatest being that it cannot stop the progress of the disease or reverse the symptoms. The only way around this flaw was to find a non-dopaminergic drug.

According to a study published few weeks ago, existing anti-malarial drugs can be made to improve the symptoms and stop the progress of the disease in laboratory rats. Nurr1 is a group of proteins that can preserve the brain’s capacity to produce dopamine, protect the existing ones from death by inflammation, and enhance their functionality. Scientists engaged in this study have discovered that anti-malarial drugs like Amodiaquine and Chloroquine can activate Nurr1 and promote its functions.

A critical deficiency of the current dopamine replacement therapy is that after a few years of administering it, patients report serious side effects like dyskinesia. In the Nurr1 study, it was found that the symptoms of the rats improved and the progression of the disease was halted without the animals exhibiting dyskinesia behaviors.

Other pharmacological approaches to treat and manage Parkinson’s disease

Another recent study suggests that a novel pharmacological approach can prevent neurodegeneration associated with Parkinson’s disease.

It has been found that degeneration of dopamine neurons in the substantia nigra region of the brain and an abnormal deposition of the alpha-synuclein protein in the other neurons from years before the manifestation of the disease are the classic features of Parkinson’s disease. Scientists also know that a specific mutation of the LRRK2 enzyme is present in about two percent of all Parkinson’s patients and that laboratory rats without this enzyme are protected from neurodegeneration even though they had an excess of alpha-synuclein.

The above-mentioned experiment was conducted on laboratory rats that had the exact mutation of the LRRK2 enzyme that is known to trigger Parkinson’s disease and an excess of ?-synuclein. Scientists discovered a class of LRRK2 inhibitors that when fed to the rats halted neurodegeneration.

Other researchers are experimenting with ways to combine pharmacological approaches to increase the effectiveness and sustainability of dopamine replacement therapy.

Several years ago it was shown that movements in Parkinson’s patients can be improved by stimulating dopaminergic receptors and inhibiting adenosine A2A receptors together. Researchers believe that adenosine A2A inhibitors should be used together with dopamine-stimulating treatments. In laboratory tests, the administration of adenosine A2A inhibitors not only improved mobility in the patients but also did not trigger the side effects that are usually associated with the L-DOPA therapy, the standard medicine used to raise dopamine levels in patients. What is more, researchers think that using adenosine A2A inhibitors will also let doctors reduce L–DOPA dosage and thus prevent the onset of side effects like severe fluctuation in dyskinase behavior that are typically associated with the drug.

A later study identified three adenosine A2A inhibitors—BIIB014, preladenant, and ST-1535—that can be used in conjunction with L-DOPA to improve the latter’s efficacy in late stages of the disease. This study also found that BIIB014 is effective on its own during the preliminary stages of the disease.

The above-mentioned breakthroughs in the treatment of Parkinson’s disease gives hope to millions. Patients suffering from other movement disorders like dystonia can also hope for a cure that will let them lead productive and meaningful lives.

References

Benninger, D., Lomarev, M., Lopez, G., Wassermann, E., Li, X., Considine, E., & Hallett, M. (2010). Transcranial direct current stimulation for the treatment of Parkinson’s disease Journal of Neurology, Neurosurgery & Psychiatry, 81 (10), 1105-1111 DOI: 10.1136/jnnp.2009.202556

Cie?lak, M., Komoszy?ski, M., & Wojtczak, A. (2008). Adenosine A2A receptors in Parkinson’s disease treatment Purinergic Signalling, 4 (4), 305-312 DOI: 10.1007/s11302-008-9100-8

Daher, J., Abdelmotilib, H., Hu, X., Volpicelli-Daley, L., Moehle, M., Fraser, K., Needle, E., Chen, Y., Steyn, S., Galatsis, P., Hirst, W., & West, A. (2015). LRRK2 Pharmacological Inhibition Abates ?-Synuclein Induced Neurodegeneration Journal of Biological Chemistry DOI: 10.1074/jbc.M115.660001

Grefkes, C., & Fink, G. (2012). Disruption of motor network connectivity post-stroke and its noninvasive neuromodulation Current Opinion in Neurology, 25 (6), 670-675 DOI: 10.1097/WCO.0b013e3283598473

Kim, C., Han, B., Moon, J., Kim, D., Shin, J., Rajan, S., Nguyen, Q., Sohn, M., Kim, W., Han, M., Jeong, I., Kim, K., Lee, E., Tu, Y., Naffin-Olivos, J., Park, C., Ringe, D., Yoon, H., Petsko, G., & Kim, K. (2015). Nuclear receptor Nurr1 agonists enhance its dual functions and improve behavioral deficits in an animal model of Parkinson’s disease Proceedings of the National Academy of Sciences, 112 (28), 8756-8761 DOI: 10.1073/pnas.1509742112

Lefaucheur JP (2006). Repetitive transcranial magnetic stimulation (rTMS): insights into the treatment of Parkinson’s disease by cortical stimulation. Neurophysiologie clinique = Clinical neurophysiology, 36 (3), 125-33 PMID: 17046607

Pinna, A. (2009). Novel investigational adenosine A receptor antagonists for Parkinson’s diseaseExpert Opinion on Investigational Drugs, 18 (11), 1619-1631 DOI: 10.1517/13543780903241615

Wu, A., Fregni, F., Simon, D., Deblieck, C., & Pascual-Leone, A. (2008). Noninvasive brain stimulation for Parkinson’s disease and dystonia Neurotherapeutics, 5 (2), 345-361 DOI: 10.1016/j.nurt.2008.02.002

Image via Ocskay Mark / Shutterstock.

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Our Mental Abilities Are Not Entirely Exceptional http://brainblogger.com/2015/07/25/our-mental-abilities-are-not-entirely-exceptional-in-animal-kingdom/ http://brainblogger.com/2015/07/25/our-mental-abilities-are-not-entirely-exceptional-in-animal-kingdom/#comments Sat, 25 Jul 2015 15:00:31 +0000 http://brainblogger.com/?p=20187 We rightfully consider ourselves the smartest species on Earth. Our smartness, however, is not entirely unique. Our mental abilities have not suddenly appeared from nowhere – they must have gradually evolved. So it does not come as a really big surprise to find out that many animals possess certain mental abilities that we traditionally considered uniquely human.

Scientists had been probing into the mental abilities of birds and animals for many years. Now we are certain that we share neuronal abilities – especially those related to language and communication – with animals.

Findings from bird studies

With its resilience and the ability to adapt to any surrounding to survive, the crow was always considered one of the most intelligent members of the avian kingdom. That was a popular belief, but now scientists have proof that crows actually have some neural structures that are similar to humans and that these neurons fire in almost the same way as ours do.

According to a study published just few weeks ago, crows have the ability to count and distinguish between numbers. In this study, scientists concentrated on a specific area of the bird’s brain, the nidopallium caudolaterale (NCL) in the endbrain region. The birds were trained to distinguish between groups with different numbers of dots shown on computer monitors. At the same times, the scientists recorded the response of “number neurons” located in the NCL region of their brains. These neurons are known to fire in the presence of numerical stimuli, presented visually or otherwise.

During the experiment, it was seen that these number neurons were activated when the bird was shown a specific number of dots. The crows were able to “distinguish” between different numbers. Being able to process abstract numbers was till now believed to be a mental feat of the highest degree. It is now evident that our numerical abilities have distinct biological roots.

The findings from another recent study on parrots yield insights into this bird’s unmatched ability to imitate vocal signals, like speech or songs. Parrots are “vocal learners,” and this study has uncovered the differences in the brains of these birds that make them superior to hummingbirds and songbirds that are also vocal learners.

Scientists knew that birds that are vocal learners have specific centers in their brains, called “cores,” that control the process of learning. According to the new findings, the parrots additionally have “shells” or “outer rings” structures in the brain to regulate the process. The study was conducted on eight varied species. They also found that these outer rings are larger in those species that are known to be better imitators than others.

What is more, these shells in a crude form were also discovered in the most ancient species of parrot they included in their experiments — the kea from New Zealand. This indicates that these brain structures date back at least 29 million years!

And wait! There are more surprises in store. During this study, scientists noted that most of the core and shell regions of the parrots overlap brain areas connected to movement. They have also discovered some peculiar gene expressions in these overlapping zones. Scientists now believe that these structural differences could explain why some parrots are able to learn to dance to tunes.

Findings from primate studies

The idea that human beings are not the only species on Earth with the unique ability to learn, imitate, and communicate has been playing on in the minds of scientists for a long time. That is why they have conducted studies on primates to understand how these seemingly intelligent animals call to and communicate with one another.

Primates like chimpanzees and gibbons happen to be exceptional linguists! For instance, chimpanzees emit calls with different pitches and volumes to indicate the presence and location of different types of fruits and especially their favorite ones.

Wild chimpanzees of Ivory Coast vary the acoustic quality of their food calls depending on the size of the fruit patch and the nutritive and energy values of the fruit. They also emitted higher-pitched calls to indicate fruits in smaller trees. The chimpanzees called loudly and excitedly when they had to indicate the presence of the Nauclea fruit. These fruits have high energy content, are big and easy to eat, and supposedly taste good. According to the scientists involved in this study, chimpanzees probably have a different call for large food finds in order to convene a gathering of their relatives so that they can socialize.

We know chimpanzees are social animals. The linguistic skills of these animals seem to complement their social behavior. Scientists know that the calls of chimpanzees vary across forests and regions. Researchers discovered that chimpanzees can pick up the ape lingo of a new region after they were relocated. A study was conducted on a group of chimpanzees that were moved from the Netherlands to the U.K. The Dutch chimpanzees preferred a particular type of apple that the English chimps did not like. The preferences of the Dutch chimps did not change upon relocation but when presented with their favorite fruit, they called out to their new mates using the Edinburgh “dialect.” It is evident that Mother Nature equipped these social animals with these sophisticated linguistic abilities so that they could mingle with and be accepted into the folds of a new group.

Our closest relatives in the animal kingdom present opportunities for scientists to trace the origins of language development in human beings. Although the neural abilities of humans, animals and birds are yet to be decoded fully, the above findings help to view our mental abilities in the larger context of animal kingdom.

References

Chakraborty, M., Walløe, S., Nedergaard, S., Fridel, E., Dabelsteen, T., Pakkenberg, B., Bertelsen, M., Dorrestein, G., Brauth, S., Durand, S., & Jarvis, E. (2015). Core and Shell Song Systems Unique to the Parrot Brain PLOS ONE, 10 (6) DOI: 10.1371/journal.pone.0118496

Ditz, H., & Nieder, A. (2015). Neurons selective to the number of visual items in the corvid songbird endbrain Proceedings of the National Academy of Sciences, 112 (25), 7827-7832 DOI: 10.1073/pnas.1504245112

Kalan, A., Mundry, R., & Boesch, C. (2015). Wild chimpanzees modify food call structure with respect to tree size for a particular fruit species Animal Behaviour, 101, 1-9 DOI: 10.1016/j.anbehav.2014.12.011

Watson, S., Townsend, S., Schel, A., Wilke, C., Wallace, E., Cheng, L., West, V., & Slocombe, K. (2015). Vocal Learning in the Functionally Referential Food Grunts of Chimpanzees Current Biology, 25 (4), 495-499 DOI: 10.1016/j.cub.2014.12.032

Image via Kletr / Shutterstock.

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Nurturing The Brain – Part 6, Resveratrol http://brainblogger.com/2015/07/23/nurturing-the-brain-part-6-resveratrol/ http://brainblogger.com/2015/07/23/nurturing-the-brain-part-6-resveratrol/#comments Thu, 23 Jul 2015 15:00:31 +0000 http://brainblogger.com/?p=20092 Resveratrol is a polyphenol found in the skin of fruit such as red grapes and berries. You may have noticed that resveratrol is all over the place right now. The hype around it is massive and it is advertised as a “wonder compound” with a myriad of benefits in disease protection, including cardiovascular diseases, cancer, diabetes, neurodegeneration, and rheumatic diseases, just to name a few.

I have briefly mentioned resveratrol when I talked about the benefits of red wine. But, as stated at the time, its naturally occurring form has a relatively low half-life in plasma and the amount of resveratrol present in many foods or beverages may be too low to lead to significant beneficial effects. Nevertheless, it may be only a matter of time until new more stable synthetic analogs of resveratrol are developed.

Is this just another fad or is resveratrol really that wondrous?

Although clinical evidence of its effects is still scarce, experimental studies on the effects of resveratrol are clearly a massive trend: a search on Pubmed reveals that more than half the research on this topic was published in the last five years.

Although there are some controversies around resveratrol (and even cases of scientific misconduct), experimental evidence does suggest that it may have interesting benefits.

Resveratrol’s effects are mostly due to its potent anti-inflammatory and antioxidant properties. Most diseases that benefit from these type of actions are therefore likely candidates for its health benefits. In cardiovascular diseases, for example, resveratrol has shown beneficial effects in animal models of hypertension, atherosclerosis, stroke, ischemic heart disease, arrhythmia, chemotherapy-induced cardiotoxicity, diabetic cardiomyopathy, and heart failure. These actions seem to be mediated by its anti-oxidant, anti-inflammatory, anti-platelet, insulin-sensitizing, and lipid-lowering properties. But clinical studies in the context of cardiovascular diseases are still limited, with conflicting results from trials having been reported.

In cancer research, also using animal models, resveratrol has been found to be effective against a number of human cancers, suggesting that it could be a useful chemotherapeutic agent, with the advantage of being well tolerated and having minimal side effects even at very high doses. Resveratrol has also shown experimental metabolic improvements, namely in glucose metabolism, body composition, liver fat accumulation, and in protection against obesity and obesity-related diseases such as type-2 diabetes. Resveratrol seems to mimic the effects of calorie restriction by regulating cellular energy homeostasis and mitochondrial biogenesis. But, again, clinical trials have had mixed results.

Resveratrol administration has also been studied on many neurological conditions. Beneficial effects on age-related neurological disorders, macular degeneration, stroke, and cognitive deficits with or without dementia have been attributed to resveratrol, most likely due to its neuroprotective action, as seen in many animal models of toxicity. In Alzheimer’s disease, for example, resveratrol has been shown to increase the clearance of amyloid-beta, and to modulate oxidative stress, neuronal energy homeostasis, cell death and longevity.

The neuroprotective actions of resveratrol have also been attributed to an effect against glutamate-induced neurotoxicity. Glutamate is a major neurotransmitter in the central nervous system that, when excessively accumulated extracellularly, can induce a calcium overload and be neurotoxic, leading to neuronal injury or death, and being associated with acute and chronic neurodegenerative diseases. Therefore, research on neuroprotective effects against glutamate-induced neurotoxicity it has been a therapeutic strategy to for treating both acute and chronic forms of neurodegeneration. In that context, resveratrol has been shown to be able to block these toxic glutamate-associated pathways.

Resveratrol has even been shown to extend the lifespan of multiple organisms, namely yeast, worms, and flies. By protecting against age-related diseases in mammals, resveratrol will most likely also have similar life-extending effects. Still, most of these actions remain to be reproduced in clinical trials.

Thanks to all the hype around resveratrol, there are now many nutritional supplements available in the market containing it. Regardless of how wonderful resveratrol may seem, beware of dietary supplements: the doses may not be adequate for an actual beneficial effect and, on the other hand, little is still know about its long-term actions. Until dose-effect clinical trials are successfully carried out and and reproduced, it is unlikely that dietary supplements will get it right.

References

Bhullar KS, & Hubbard BP (2015). Lifespan and healthspan extension by resveratrol. Biochimica et biophysica acta, 1852 (6), 1209-1218 PMID: 25640851

Bitterman JL, & Chung JH (2015). Metabolic effects of resveratrol: addressing the controversies. Cellular and molecular life sciences : CMLS, 72 (8), 1473-88 PMID: 25548801

de Ligt M, Timmers S, & Schrauwen P (2015). Resveratrol and obesity: Can resveratrol relieve metabolic disturbances? Biochimica et biophysica acta, 1852 (6), 1137-1144 PMID: 25446988

Pasinetti GM, Wang J, Ho L, Zhao W, & Dubner L (2015). Roles of resveratrol and other grape-derived polyphenols in Alzheimer’s disease prevention and treatment. Biochimica et biophysica acta, 1852 (6), 1202-1208 PMID: 25315300

Poulsen MM, Fjeldborg K, Ornstrup MJ, Kjær TN, Nøhr MK, & Pedersen SB (2015). Resveratrol and inflammation: Challenges in translating pre-clinical findings to improved patient outcomes. Biochimica et biophysica acta, 1852 (6), 1124-1136 PMID: 25583116

Singh CK, Ndiaye MA, & Ahmad N (2015). Resveratrol and cancer: Challenges for clinical translation. Biochimica et biophysica acta, 1852 (6), 1178-1185 PMID: 25446990

Szkudelski T, & Szkudelska K (2015). Resveratrol and diabetes: from animal to human studies. Biochimica et biophysica acta, 1852 (6), 1145-1154 PMID: 25445538

Zhang LN, Hao L, Wang HY, Su HN, Sun YJ, Yang XY, Che B, Xue J, & Gao ZB (2015). Neuroprotective effect of resveratrol against glutamate-induced excitotoxicity. Advances in clinical and experimental medicine : official organ Wroclaw Medical University, 24 (1), 161-5 PMID: 25923101

Zordoky BN, Robertson IM, & Dyck JR (2015). Preclinical and clinical evidence for the role of resveratrol in the treatment of cardiovascular diseases. Biochimica et biophysica acta, 1852 (6), 1155-1177 PMID: 25451966

Image via Aimee M Lee / Shutterstock.

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High-Intensity Interval Training And Brain Health http://brainblogger.com/2015/07/19/high-intensity-interval-training-and-brain-health/ http://brainblogger.com/2015/07/19/high-intensity-interval-training-and-brain-health/#comments Sun, 19 Jul 2015 15:00:25 +0000 http://brainblogger.com/?p=20095 A lot has been said about the effects of exercise on brain health. Just like diets, exercise patterns are highly susceptible to pop culture’s trends and fads. A huge trend from the last few years is High-Intensity Interval Training (HIIT). You can find these exercise protocols in most gyms and all over the internet. And there is a surprising amount of research on HIIT’s health effects, mostly on cardiovascular health.

What is high-intensity interval training?

HIIT, also called high-intensity intermittent exercise or sprint interval training, is a form of interval training. It’s an intermittent exercise protocol wherein periods of short but intense anaerobic exercise are alternated with less intense recovery periods.

This actually reminds me of intermittent energy restriction diets and, in fact, there is a common anthropologic argument favoring both: the survival of our species has relied greatly on the ability to acquire food; our hunter-gatherer ancestors will most likely have required a high level of physical performance mostly based on intermittent running while hunting for food. Therefore, our bodies may have adapted to such patterns of energetic challenges. Our current sedentary lifestyle has consequently rendered us susceptible to a great deal of diseases.

Physical inactivity is one of the top ten risk factors for poor health, being associated with an increased risk of premature cardiovascular and cerebrovascular diseases. Exercise, on the other hand, is known to benefit the brain by promoting angiogenesis (new blood vessel formation), neurogenesis, and synaptic plasticity, thereby improving cerebral blood flow and metabolism and counteracting age-associated cognitive decline and dementia.

From among the available studies on the health benefits of HIIT, one was particularly eye-catching: a review article on HIIT and cerebrovascular health published on the Journal of Cerebral Blood Flow and Metabolism.

HIIT and cerebrovascular health

As said above, different types of exercise may have a different impact on brain health; optimizing exercise in order to prevent stroke and associated neurovascular diseases would therefore be desirable in that context. This review thus focused on analyzing to what extent HIIT could impact cerebrovascular function.

When compared to moderate-intensity continuous exercise training, HIIT seems to confer similar or even higher metabolic, cardiac, and systemic vascular health benefits, both in healthy and in patients with cardiovascular diseases or hypertension.

In fact, one study has shown that HIIT had twice the effect of moderate-intensity continuous exercise in lowering blood pressure. Given that hypertension is a paramount risk factor for stroke, it seems likely that HIIT may also be beneficial in preventing stroke. However, research on the impact and potential benefits of HIIT on cerebral blood flow are rather scarce. It is unknown whether HIIT may have any detrimental effects on the brain. The potential dangers of HIIT to the brain include any consequences that a rapid increase in systemic blood pressure may have, which include the risk of hyperperfusion injury that could lead to stroke or blood–brain barrier breakthrough. But this is all speculative since there is no clinical research examining the effects of HIIT on the brain.

Still, the study states that patients with neurological pathologies, such as Parkinson’s disease and stroke have already begun using HIIT-based protocols. So far, no adverse effects have been reported for stroke rehabilitation but there are still too few studies to make firm conclusions. Nevertheless, given the relationship between heart disease and stroke it seems likely that the beneficial cardiovascular effects of HIIT may indeed be a benefit for cerebrovascular function.

In the end, regardless of the exercise protocol, what really benefits the brain is to remain physically active.

References

Colcombe SJ, Erickson KI, Scalf PE, Kim JS, Prakash R, McAuley E, Elavsky S, Marquez DX, Hu L, & Kramer AF (2006). Aerobic exercise training increases brain volume in aging humans. The journals of gerontology. Series A, Biological sciences and medical sciences, 61 (11), 1166-70 PMID: 17167157

Lautenschlager NT, Cox K, & Cyarto EV (2012). The influence of exercise on brain aging and dementia. Biochimica et biophysica acta, 1822 (3), 474-81 PMID: 21810472

Lista I, & Sorrentino G (2010). Biological mechanisms of physical activity in preventing cognitive decline. Cellular and molecular neurobiology, 30 (4), 493-503 PMID: 20041290

Lucas SJ, Cotter JD, Brassard P, & Bailey DM (2015). High-intensity interval exercise and cerebrovascular health: curiosity, cause, and consequence. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism, 35 (6), 902-911 PMID: 25833341

Murray CJ, & Lopez AD (2013). Measuring the global burden of disease. The New England journal of medicine, 369 (5), 448-57 PMID: 23902484

Vaynman S, & Gomez-Pinilla F (2006). Revenge of the “sit”: how lifestyle impacts neuronal and cognitive health through molecular systems that interface energy metabolism with neuronal plasticity. Journal of neuroscience research, 84 (4), 699-715 PMID: 16862541

Image via EpicStockMedia / Shutterstock.

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Best and Worst of Neuroscience and Neurology – June 2015 http://brainblogger.com/2015/07/12/best-and-worst-of-neuroscience-and-neurology-june-2015/ http://brainblogger.com/2015/07/12/best-and-worst-of-neuroscience-and-neurology-june-2015/#comments Sun, 12 Jul 2015 12:37:59 +0000 http://brainblogger.com/?p=20089 Significant numbers of interesting findings in both theoretical neurobiology and in more practical applications aimed at studying various brain conditions and diseases have been published this month. Choosing the most interesting articles to include in this monthly review is a highly subjective exercise. As usual, the content of this article mostly reflects my personal opinion about their significance.

On 9 June, the scientific community marked 140 years since the birth of Sir Henry Dale. Sir Dale is credited for identification of achetylcholine as a potential neurotransmitter back in 1914. The role of acetylcholine in nervous system was later confirmed by Otto Loewi, and both scientists shared the Nobel Prize for Medicine in 1936. The discovery is still considered a foundation stone for our understanding of signal transmission in nervous system.

THE BEST

Mental flexibility and the function of rare neurons

We all know that some people are flexible in their behavior and can quickly adapt to the changing environments, while others are very slow at recognizing that the rules have changed and continue sticking to the old “time-proven” norms.

Researchers have now found that this mental flexibility, or the lack of such, is not just a psychological phenomenon but is linked to the function of certain rare neurons in the brain. Cholinergic interneurons that represent only 1% of neurons in the striatum turn out to play a key role in this behavioral flexibility. The striatum is a part of the brain involved in the higher-level decision-making.

In their experiments, researchers trained rats to claim food rewards by reacting to certain external signals. After this, they destroyed cholinergic interneurons in some rats and changed the type of stimulus, leading to a better reward. Normal rats were able to quickly find out which strategy led to receiving the food. However, the animals with damaged cholinergic interneurons were unable to change their behavior and kept using the previously learned tricks for getting the rewards even though they were very ineffective. It remains to be seen how the function of cholinergic interneurons in humans correlates with individual mental flexibility.

Bad diet affects mental flexibility

Cognitive flexibility was the subject of another interesting study that analyzed the link between high-fat and high-sugar diets and mental functions.

It turned out that after just four weeks on these unhealthy diets, especially on the diet rich in sugar, the performance of experimental animals on various mental and physical tests started to decrease. Cognitive flexibility – the ability to adjust behavior to the changing circumstances – was particularly affected. Rats demonstrated serious decline in their learning abilities, as well as worsening short- and long-term memory. Scientists believe that this is a result of changes in the gut flora that take place during the expended periods of unhealthy eating. The findings confirm once again the importance of the crosstalk between the bacterial flora in the gut and our brain functions.

Genetic link between creativity and mental disorders

It is already proven that there is a link between creativity and higher risk of some mental disorders such as bipolar disorder and schizophrenia. What remained unknown until now is whether this link has any genetic component, or the connection exists due to socio-psychological reasons and environmental factors. New findings published by researchers from King’s College London have now confirmed that creativity and some mental disorders do have common genetic roots.

Scientists analyzed the genetic data from over 86,000 individuals from Iceland and found that the genes linked to schizophrenia and bipolar disorders are indeed much more common in the individuals defined as creative. It appears that creative people do have genetic predisposition to thinking differently. Combined with negative environmental factors, this predisposition can lead to the development of mental illnesses.

Sleep model in a Petri dish

Despite decades of research, sleep remains a mystery. We don’t know why we sleep or what purpose sleeping serves and very little is known about biochemical and physiological mechanisms involved in sleep. This makes a new discovery of scientists from the Washington State University particularly important.

The researchers managed to isolate and grow in the Petri dish a small group of neurons that exhibit a typical sleep and wake behavior depending on the experimental conditions. The network of cells in the mature culture displays the same EEG patterns that can be observed in the whole brain. For a long time it was believed that sleep is a whole-brain phenomenon. Now it is becoming apparent that parts of the brain and even small neuronal network can “fall asleep” independently. The discovery will help to study the genetic and biochemical aspects of the sleep in a small laboratory model without intrusions into the whole brains.

Another twist in the placebo story

The use of placebo is a mainstream approach in the clinical trials of new drug. The amazing thing is that a placebo (a fake pill filled with some innocent ingredients) often works. Although nobody knows exactly how it works, scientists believe that a simple expectation of positive effect is sufficient to achieve certain improvements. This belief, however, may not be entirely correct.

In a series of recent experiments, researchers gave placebo pills to people with various conditions and told them that the pills were fakes. Nonetheless, they still produced improvements for a seriously large number of patients. Irritable bowel syndrome, depression and migraine are some of the conditions where this effect has been demonstrated. There is no explanation to this phenomenon yet. However, new neurophysiological studies reveal neurotransmitter pathways that mediate placebo effects. There is evidence that genetic variations in these pathways can modify placebo effects in individuals.

THE WORST

It is not rare to see scientific theories to be proven wrong. However, the negative results are often informative and help to get a better picture of a problem in question.

Social phobia is caused but excess of serotonin, not its shortage

Rather unexpected results were obtained this month by researchers studying social anxiety disorder. It was generally believed that people with social phobia produce too little serotonin in the brain. Therefore, treatment involves the use of SSRIs (selective serotonin re-uptake inhibitors), which increase the amount of serotonin by inhibiting its reabsorption back into the presynaptic cells. Using a special tracer, the researchers found that the situation is exactly opposite – patients with social anxiety disorder produce excessive amounts of serotonin, and also pump back more of this neurotransmitter. The finding may have major implications for treating this condition.

Mental activity does not prevent the development of Alzheimer’s signs in brain

A number of recent studies point to the fact that keeping body and mind active may protect against the development of Alzheimer’s disease. However, novel data cast certain doubts on this emerging view. Researchers found that keeping active has no influence on the biochemical markers of Alzheimer’s, such as amyloid-beta deposit, which remains on the same level regardless of the patients activity level. However, more active people clearly performed better in the cognitive tests and had higher IQ level. It is likely that mental and physical activity triggers some compensatory mechanisms that prevent or slow down the disease manifestation, even when the underlying physiological changes take place.

Parkinson’s disease probably starts in the gut, not the brain

Like with many other neurodegenerative disorders, it is not clear why, how and when Parkinson’s disease starts. New data suggest that the disease originates not in the brain, as previously thought, but in the gut. This conclusion is based on an interesting observation of researchers from Denmark. The scientists noticed that the incidence of Parkinson’s disease is much lower among people who underwent vagotomy, a surgical treatment for ulcer that involves severing of the vagus nerve. This nerve connects the gastrointestinal tract with the brain. It is known that many Parkinson’s patients had history of gastrointestinal problems before the onset of the disease. So it appears that Parkinson’s disease initially develops in the gut and later spreads to the brain via the vagus nerve.

General anesthesia is harmful for young children’s brain

It was always suspected but now this is official: the use of surgical anesthesia in young children has a negative effect on their brain structure and mental abilities later in life. In their retrospective study of children who underwent surgery under general anesthesia before age 4, researchers from Cincinnati Children’s Hospital Medical Center reported that these children had lower IQ, diminished language comprehension and lower density of grey matter in the posterior region of the brain.

Although all these parameters still remain within the normal range, statistically they are lower than in children who didn’t experience anesthesia at this young age. The findings highlight the need to develop better approaches to surgical anesthesia for young children.

Some MRI contrast agents might be dangerous

With millions of patients getting MRI scans every year, the technique rapidly becomes one of the most commonly used diagnostic tools in the developed countries. However, new data published this month cast the shadow on the safety of the contrast agents used for the data acquisition – so-called linear-type gadolinium-based contrast agents.

It appears that repeated use of these agents in the MRI scans lead to accumulation of toxic heavy metal gadolinium in the patients’ brains. The safety concerns may have serious implication on the whole MRI industry and likely to result in substituting linear-type agents with safer and more stable macrocyclic gadolinium-based agents. The use of the latter does not lead to accumulation of gadolinium in the brain.

References

Aoki, S., Liu, A., Zucca, A., Zucca, S., & Wickens, J. (2015). Role of Striatal Cholinergic Interneurons in Set-Shifting in the Rat Journal of Neuroscience, 35 (25), 9424-9431 DOI: 10.1523/JNEUROSCI.0490-15.2015

Backeljauw, B., Holland, S., Altaye, M., & Loepke, A. (2015). Cognition and Brain Structure Following Early Childhood Surgery With Anesthesia PEDIATRICS, 136 (1) DOI: 10.1542/peds.2014-3526

Frick, A., Åhs, F., Engman, J., Jonasson, M., Alaie, I., Björkstrand, J., Frans, ?., Faria, V., Linnman, C., Appel, L., Wahlstedt, K., Lubberink, M., Fredrikson, M., & Furmark, T. (2015). Serotonin Synthesis and Reuptake in Social Anxiety Disorder JAMA Psychiatry DOI: 10.1001/jamapsychiatry.2015.0125

Gidicsin, C., Maye, J., Locascio, J., Pepin, L., Philiossaint, M., Becker, J., Younger, A., Dekhtyar, M., Schultz, A., Amariglio, R., Marshall, G., Rentz, D., Hedden, T., Sperling, R., & Johnson, K. (2015). Cognitive activity relates to cognitive performance but not to Alzheimer disease biomarkers Neurology, 85 (1), 48-55 DOI: 10.1212/WNL.0000000000001704

Hall, K., Loscalzo, J., & Kaptchuk, T. (2015). Genetics and the placebo effect: the placebome Trends in Molecular Medicine, 21 (5), 285-294 DOI: 10.1016/j.molmed.2015.02.009

Jewett, K., Taishi, P., Sengupta, P., Roy, S., Davis, C., & Krueger, J. (2015). Tumor necrosis factor enhances the sleep-like state and electrical stimulation induces a wake-like state in co-cultures of neurons and glia European Journal of Neuroscience DOI: 10.1111/ejn.12968

Magnusson, K., Hauck, L., Jeffrey, B., Elias, V., Humphrey, A., Nath, R., Perrone, A., & Bermudez, L. (2015). Relationships between diet-related changes in the gut microbiome and cognitive flexibility Neuroscience, 300, 128-140 DOI: 10.1016/j.neuroscience.2015.05.016

Power, R., Steinberg, S., Bjornsdottir, G., Rietveld, C., Abdellaoui, A., Nivard, M., Johannesson, M., Galesloot, T., Hottenga, J., Willemsen, G., Cesarini, D., Benjamin, D., Magnusson, P., Ullén, F., Tiemeier, H., Hofman, A., van Rooij, F., Walters, G., Sigurdsson, E., Thorgeirsson, T., Ingason, A., Helgason, A., Kong, A., Kiemeney, L., Koellinger, P., Boomsma, D., Gudbjartsson, D., Stefansson, H., & Stefansson, K. (2015). Polygenic risk scores for schizophrenia and bipolar disorder predict creativity Nature Neuroscience, 18 (7), 953-955 DOI: 10.1038/nn.4040

Robert, P., Lehericy, S., Grand, S., Violas, X., Fretellier, N., Idée, J., Ballet, S., & Corot, C. (2015). T1-Weighted Hypersignal in the Deep Cerebellar Nuclei After Repeated Administrations of Gadolinium-Based Contrast Agents in Healthy Rats Investigative Radiology, 50 (8), 473-480 DOI: 10.1097/RLI.0000000000000181

Svensson, E., Horváth-Puhó, E., Thomsen, R., Djurhuus, J., Pedersen, L., Borghammer, P., & Sørensen, H. (2015). Vagotomy and subsequent risk of Parkinson’s disease Annals of Neurology DOI: 10.1002/ana.24448

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Forgetting Names? Go to Sleep! http://brainblogger.com/2015/07/05/forgetting-names-go-to-sleep/ http://brainblogger.com/2015/07/05/forgetting-names-go-to-sleep/#comments Sun, 05 Jul 2015 14:00:53 +0000 http://brainblogger.com/?p=20002 Can’t remember where you keep things? Seem to forget names and appointments more often than before? Don’t blame your failing memory on age. It is more likely that you are not getting your quota of beauty sleep.

In an age of distractions (read: smartphone, social media, and TV) and trying to get too many things done in too little time, we often forego sleep. The result is not just dark circles under the eyes or yawning our heads off the next day in office. We also tend to forget more the less we sleep. Yes, scientists have cracked one more sleep code; sleep helps us form and cement long-term memories.

What does sleep do to our brains?

We don’t need to be told about the restorative effects of sleep because we wake up feeling rested and refreshed after a good night’s sleep. Psychological studies have always hinted that sleep helps form and cement memories by preventing mental and behavioral activities from interfering during the consolidation process. But now for the first time, scientists have decoded what happens inside our brains, at the synaptic level, when we sleep.

According to a recent report, sleep stimulates the brain cells to respond in two different ways. The synaptic connections either get strengthened, which facilitates long-term retention of memories, or get weakened, which leads to forgetting. The process of strengthening the memory is known as long-term potentiation (LTP) or consolidation. Scientists have identified a specific phosphorylated protein that influences LTP.

This study builds upon and bolsters a series of earlier studies carried out to determine the relationship between sleep and memory formation and consolidation.

According to another study, enduring memory formation is facilitated by rehearsing previously-learned matter. Much of this rehearsal takes place without us knowing it, which is when we sleep.

Some other studies hint at the role of dopamine in forming and consolidating memories and how sleep affects dopaminergic activity. A decrease in dopaminergic signaling improves the memory retention and consolidation process while an increase accelerates forgetting. These findings are in line with what scientists had discovered in earlier studies: there is less external and internal stimulation to activate dopamine neurons when a person is asleep, so there is less dopaminergic activity during sleep.

Sleep, memory and learning

Memory retention, consolidation, and retrieval are integral processes without which learning cannot take place. The findings from the earlier-mentioned studies make us curious about the implications of sleep on the learning process. Or as students would be curious to know—should I stay up late and cram for tomorrow’s exams or go to sleep?

According to a study carried out on laboratory mice, learning triggers the growth of spines on different dendritic branches. These spines correspond to new neuronal connections that form in response to learning new tasks. In the laboratory, two groups of mice were made to learn how to run on a spinning rod. Then one group of mice slept for 7 hours while the other group remained awake. After waking up, it was found that the mice that had slept had more dendritic spine growth than the animals that did not sleep.

Sleep and memory reorganization

Sleep not only consolidates memory and aids learning. It also reorganizes memories and reconfigures details that promote creativity. Qualitative reorganization of memories leads to the formation of new memories or associations that the subjects have not learned previously. This leads to creative and unique insights into a situation.

Sleep and false memory formation

There are several aspects of memory. Learning is considered effective not only when we retain what we have learned but also when we can reproduce or recall the learning matter accurately after a certain period of time. Memory may sometimes play tricks on us by distorting memories. This means that we sometimes “remember” events and experiences that have never occurred. Scientists have discovered a link between sleep and false memory formation.

According to one study, some types of memories degenerate over time and in response to sleep and lead to the formation of false memories. In this study, the subjects were made to study lists of words with similar semantic associations, like door, ledge, sill, curtain, house, shade, and so on. After a gap of two days, they were tested on their memory of the words. When prompted with cues, they also “remembered” a critical word that was not included in the original list. What is more, this false memory persisted the longer the gap was between memory formation and recall.

This indicates that sleep affects different types of memories differently. The difference stems from the specific location in the brain where a particular memory is processed.

Memories that are processed by the hippocampal region are consolidated more effectively after a period of deep sleep. But memory consolidation that requires semantic processing, as when we have to remember related words, takes place in the left ventrolateral prefrontal cortex and the left lateral temporal cortex. So, not all memories are improved by sleep.

Implications of the sleep-memory studies

We live in busy times where we are stretched too thin and get pulled in all directions. The first casualty is sleep. Everyone should take note of the findings from the above-mentioned studies. It is evident that sleep improves learning by helping consolidate memories.

So students should not push themselves to forego sleep to study till the wee hours. Educators and teachers should organize the curriculum such that students do not feel burdened by the amount of material they have to study. Curriculum developers may also consider revamping the pattern of assessments so that these test the analytical abilities of the students rather than their capacity for rote learning.

Professionals should minimize distractions and organize their lives so that they are not compelled to stay up late to prepare presentations or learn new concepts and skills relevant to their jobs.

The studies on the relation between sleep and memory provide critical insights into how to make the learning process more effective. Do not skimp on the shut-eye!

References

Berry, J., Cervantes-Sandoval, I., Nicholas, E., & Davis, R. (2012). Dopamine Is Required for Learning and Forgetting in Drosophila Neuron, 74 (3), 530-542 DOI: 10.1016/j.neuron.2012.04.007

Berry, J., Cervantes-Sandoval, I., Chakraborty, M., & Davis, R. (2015). Sleep Facilitates Memory by Blocking Dopamine Neuron-Mediated Forgetting Cell, 161 (7), 1656-1667 DOI: 10.1016/j.cell.2015.05.027

Blanco, W., Pereira, C., Cota, V., Souza, A., Rennó-Costa, C., Santos, S., Dias, G., Guerreiro, A., Tort, A., Neto, A., & Ribeiro, S. (2015). Synaptic Homeostasis and Restructuring across the Sleep-Wake Cycle PLOS Computational Biology, 11 (5) DOI: 10.1371/journal.pcbi.1004241

Landmann, N., Kuhn, M., Piosczyk, H., Feige, B., Baglioni, C., Spiegelhalder, K., Frase, L., Riemann, D., Sterr, A., & Nissen, C. (2014). The reorganisation of memory during sleep Sleep Medicine Reviews, 18 (6), 531-541 DOI: 10.1016/j.smrv.2014.03.005

Oudiette, D., Antony, J., Creery, J., & Paller, K. (2013). The Role of Memory Reactivation during Wakefulness and Sleep in Determining Which Memories Endure Journal of Neuroscience, 33 (15), 6672-6678 DOI: 10.1523/JNEUROSCI.5497-12.2013

Payne, J., Schacter, D., Propper, R., Huang, L., Wamsley, E., Tucker, M., Walker, M., & Stickgold, R. (2009). The role of sleep in false memory formation Neurobiology of Learning and Memory, 92 (3), 327-334 DOI: 10.1016/j.nlm.2009.03.007

Yang, G., Lai, C., Cichon, J., Ma, L., Li, W., & Gan, W. (2014). Sleep promotes branch-specific formation of dendritic spines after learning Science, 344 (6188), 1173-1178 DOI: 10.1126/science.1249098

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The Neurology of Anxiety in Times of Critical Decision-Making http://brainblogger.com/2015/07/01/the-neurology-of-anxiety-in-times-of-critical-decision-making/ http://brainblogger.com/2015/07/01/the-neurology-of-anxiety-in-times-of-critical-decision-making/#comments Wed, 01 Jul 2015 14:00:46 +0000 http://brainblogger.com/?p=20020 Scientists have identified the specific neural circuitry that triggers anxiety in individuals when confronted with critical decisions. Our brains can actually gauge how critical a decision is and trigger anxiety in us accordingly!

Do you freak out when you have to decide if you want to order pizza or a tub of fried chicken for dinner? No? But you definitely get anxious when you have to decide between schools for your kid or figure out which job offer to accept — the one that will keep you tied to your desk and pay you a hefty paycheck or the one that promises a lot of adventure for peanuts. There is a reason why we get anxious when we have to make certain decisions, and why we decide on other matters without batting an eyelid. The reason is inside the brain.

A mystery solved leads to a discovery

It was pure chance that led scientists to stumble upon the fact that the human brain processes decision-making activities of varying degrees of criticality in different regions. They had started out trying to find out the exact role of striosomes.

Striosomes are bunches of cells scattered throughout the striatum. The striatum is responsible for coordinating our movements and processing emotions. Scientists believed that the striosomes had a hand in the development of certain disorders in humans. But they couldn’t be certain till they had pinpointed the role of these cells.

They also had a hunch that the striosomes play a role in processing emotions because some regions of the prefrontal cortex extend into the striatum. The role of the prefrontal cortex in evaluating stimuli and triggering appropriate emotional responses is well-documented, as evident from the following two studies.

According to one of the studies, different regions of the medial prefrontal cortex (mPFC) contribute equally to facilitate the normal processing of emotions. The dorsal-caudal region of the mPFC is activated in response to negative stimuli while the ventral-rostral portion is responsible for regulating emotional responses.

According to the findings of another study, the ventromedial prefrontal cortex region is involved in the ability of a person to normally differentiate between right and wrong. The study suggests that in cases of certain moral dilemmas, these judgments are influenced by emotions. The study was carried out on persons with damage to the ventromedial prefrontal cortex regions of their brains. It was found that these people displayed abnormal judgment patterns that were devoid of emotional considerations when confronted with situations that presented moral dilemmas.

Based on the above findings and those from other studies, scientists were now curious to know if and how striosomes influence emotions. In an experiment on laboratory mice, the animals were made to choose between two options. In one scenario, the rats could choose a strong-smelling and intensely-flavored chocolate but, in turn, they would be subjected to bright light that they don’t like. In the other scenario, the light was not so bright, but the chocolate was also weak. Clearly, this approach-avoidance scenario was stressful for the animals and they experienced anxiety.

The rats were also made to go through other tests that were not so stressful, so they were less anxious at these times.

In the chocolate-light experiment, it was found that the cortex-striosomes circuit was activated when the rats had to make the decision. But this circuit remained inert in the other less-stressful tests.

When the scientists disrupted the flow of signals between the cortex and the striosomes in the chocolate-light experiment, the rats chose the high-risk, high-reward (strong chocolate-bright light) option 20 percent more than when the flow of input was not interfered with. When the striosomes were forcefully activated by bombarding them with sensory inputs, the rats chose the high-risk, high-reward option less often.

Neuroeconomic studies to find out how humans make decisions had hinted that anxiety and decision-making share neural networks that involve brain regions like the striatum, the ventromedial PFC, the dorsolateral PFC, and the amygdala. This overlap of the brain systems indicates that negative emotions like fear and anxiety determine how an individual calculates value before making a choice. At that time, the scientists were unsure how the circuit worked. Now they know!

The framing effect

Another study points out to the role of the “framing effect” during decision-making activities and how it triggers anxieties.

Individuals also tend to make decisions based on the outcomes they perceive—in terms of gains and losses. That is, how the outcomes are framed — positively or negatively — can greatly influence their decisions in stressful situations. The normal human reaction is to choose positively-framed options and avoid the negative ones. In this study, it was found that the subjects did the opposite (chose the negatively-framed options and avoided the positive ones) when the dorsomedial and dorsolateral PFC regions of their brains along with the anterior cingulate cortex were activated.

Implications of the recent findings

The latest findings that clearly establish how certain decision-making situations can trigger anxiety in individuals have widespread implications. A keen understanding of the neural connections and the associated relationships can help scientists find more effective ways to manage the symptoms of psychiatric disorders like schizophrenia and borderline personality disorder where the decision-making capability of the patient is severely impaired.

The above findings also suggest a possibility that scientists can consider looking into – the relationship between people suffering from anxiety disorders and their tendency to avert risks.

Additionally, these findings should interest psychiatrists and counselors in devising therapies for their patients suffering from anxiety disorders. People suffering from severe anxiety tend to avoid situations that they perceive to be threatening and make decisions accordingly. Such behavioral traits and coping mechanisms can negatively impact on the quality of their lives. The identification of the neural circuitry that governs anxiety response in the face of decision-making and how it works can provide clues to medicine-makers when they try to come up with drug therapies.

References

Etkin, A., Egner, T., & Kalisch, R. (2011). Emotional processing in anterior cingulate and medial prefrontal cortex Trends in Cognitive Sciences, 15 (2), 85-93 DOI: 10.1016/j.tics.2010.11.004

Friedman, A., Homma, D., Gibb, L., Amemori, K., Rubin, S., Hood, A., Riad, M., & Graybiel, A. (2015). A Corticostriatal Path Targeting Striosomes Controls Decision-Making under Conflict Cell, 161 (6), 1320-1333 DOI: 10.1016/j.cell.2015.04.049

Hartley, C., & Phelps, E. (2012). Anxiety and Decision-Making Biological Psychiatry, 72 (2), 113-118 DOI: 10.1016/j.biopsych.2011.12.027

Jepma, M., & Lopez-Sola, M. (2014). Anxiety and Framing Effects on Decision Making: Insights from Neuroimaging Journal of Neuroscience, 34 (10), 3455-3456 DOI: 10.1523/JNEUROSCI.5352-13.2014

Koenigs, M., Young, L., Adolphs, R., Tranel, D., Cushman, F., Hauser, M., & Damasio, A. (2007). Damage to the prefrontal cortex increases utilitarian moral judgements Nature, 446 (7138), 908-911 DOI: 10.1038/nature05631

Image ID: 147180335

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The Causes Of Alzheimer’s Disease – An Overview http://brainblogger.com/2015/06/30/the-causes-of-alzheimers-disease-an-overview/ http://brainblogger.com/2015/06/30/the-causes-of-alzheimers-disease-an-overview/#comments Tue, 30 Jun 2015 14:00:03 +0000 http://brainblogger.com/?p=19889 Dementia is characterized by a progressive and debilitating decline in cognition, function and behavior. Its numbers are staggering: according to the World Health Organization, the total number of people with dementia worldwide in 2010 was estimated at 35.6 million and predicted to nearly double every 20 years, to 65.7 million in 2030 and 115.4 million in 2050.

Each year, there are around 7.7 million new cases of dementia, implying one new case every four seconds. Its incidence rate increases exponentially with age, with the highest increase occurring after 70 years of age.

Alzheimer’s disease (AD) is the most common form of dementia worldwide, accounting for around 70% of dementia cases, with North America and Western Europe having the highest prevalence and incidence rates.

Healthcare costs for AD are massive: in the US alone, the estimated healthcare costs are of $172 billion per year. Despite these striking numbers and the extensive amount of research being conducted on AD, its exact pathological mechanisms remain to be determined, with a number of theories having been proposed. Risk factors for AD development include genetic factors, cerebrovascular disease, traumatic brain injury, hypertension, type 2 diabetes, obesity, and smoking. Neuroprotective factors include adequate diets, exercise and intellectual activity.

Hallmarks of the disease

There are some pathological features in AD brain tissue that are considered hallmarks of the disease. Specifically, amyloid plaques – extracellular deposits of the amyloid-beta (A-beta) peptide – and neurofibrillary tangles, intracellular accumulations of the hyperphosphorylated tau (p-tau), a microtubule assembly protein. Other characteristic changes include increased microglial reactivity and widespread loss of neurons, white matter and synapses.

Despite considerable controversy, the predominant line of research in AD has followed the amyloid hypothesis for the pathophysiology of AD, which claims that it is the A-beta peptide that causes AD and that neu­rofibrillary tangles, cell loss, vascular damage and dementia are a direct consequence of A-beta deposition.

However, evidence supporting this theory is not totally clear. In May, Nature Neuroscience published an interesting perspective article that overviews the arguments for and against this theory.

Supporting the amyloid hypothesis

According to the mentioned article, the strongest evidence supporting the role of A-beta as AD initiator comes from human genetics. There is a form of familial AD that is caused by mutations in genes which are directly involved in A-beta production, namely the gene that encodes the precursor to A-beta, the amyloid precursor protein (APP), and the genes that encode Presenilin 1 and 2, subunits of the complex that cleaves APP to generate A-beta. These mutations induce an enhanced accumulation of amyloid plaques.

In sporadic forms of AD the strongest genetic risk factor is apolipoprotein E (ApoE), mainly produced by astrocytes in the brain, and that is responsible for transporting cholesterol to neurons via ApoE receptors. There are different alternative forms of the APOE gene, each having different effects in the risk of AD development. ApoE3 is the most common form, ApoE2 decreases the risk of AD development, and ApoE4 is known to increase the risk for AD.

An estimated 20–25% of the population carries at least one copy of ApoE4, having an increased risk of AD of around 4-fold; in the  2% of the population that carries two E4 copies, on the other hand, the increased risk is of around 12-fold. Experimental studies have shown that ApoE4 does indeed promote A-beta aggregation and deposition and that the reduction of ApoE levels can decrease amyloid plaque development.

Against the amyloid hypothesis

The tau protein is regarded as essential for AD-associated neurodegeneration. Arguments against the amyloid theory stem from the fact that there are anatomic and temporal mismatches between A-beta pathology, p-tau aggregation and neurodegeneration in AD.

For instance, A-beta deposition occurs first and most severely in regions that do not match those where neuronal death is first observed, whereas tau pathology correlates much more closely with neuronal loss, not only anatomically, but also temporally, since many clinically asymptomatic individuals are known to already have extensive amyloid plaque pathology.

One explanation presented in the mentioned article is that, in addition to amyloid plaques, A-beta can be present in the form of small molecular complexes (oligomers) that can mediate AD pathol­ogy. These oligomeric A-beta molecules can actually be found in brain regions showing extensive neuronal loss, and their presence seems to correlate more extensively with the development of dementia than the presence of amyloid plaques. Indeed, A-beta oligomers seem to accumulate with age, and be correlated with tau pathology in humans.

Therefore, a proposed model for AD pathology places A-beta as the primary initiator of AD: age-associated factors may induce oligomeric and fibrillar A-beta accumulation, leading to the appearance of the first plaques; after several years of A-beta aggregation, it somehow triggers the tau pathology, with neurofibrillary tangles, as well as other toxic proteins such as synuclein beginning to accumulate, prompting increased neurodegeneration. At this point, the degenerative changes become extensive, with neuronal loss, oxidative damage, inflammation, and clinical symptoms becoming evident.

What seems unclear is what induces the aggregation and accumulation of A-beta in the first place and how it is related to age. It is possible that multiple factors that may enhance A-beta production and aggregation or suppress its clearance can contribute to this throughout life.

In what concerns AD therapy, it seems that when the disease becomes clearly symptomatic, treatments are less likely to have any major effects. Ideally, preventative strate­gies for AD would be the best approach, and therapies should be delivered as early in the process as possi­ble; treatment options should focus on conditions that may induce the onset of A-beta accumulation in middle age. Monitoring the appearance of positive A-beta biomarkers would be invaluable for detecting the first signs of disease development and initiating therapeutic strategies.

References

Bettens K, Sleegers K, & Van Broeckhoven C (2013). Genetic insights in Alzheimer’s disease. The Lancet. Neurology, 12 (1), 92-104 PMID: 23237904

Duthey B (2013). Priority Medicines for Europe and the World Update Report, Background Paper 6.11 – Alzheimer Disease and other Dementias. World Health Organization.

Ferri CP, Prince M, Brayne C, Brodaty H, Fratiglioni L, Ganguli M, Hall K, Hasegawa K, Hendrie H, Huang Y, Jorm A, Mathers C, Menezes PR, Rimmer E, Scazufca M, & Alzheimer’s Disease International (2005). Global prevalence of dementia: a Delphi consensus study. Lancet, 366 (9503), 2112-7 PMID: 16360788

Musiek ES, & Holtzman DM (2015). Three dimensions of the amyloid hypothesis: time, space and ‘wingmen’. Nature neuroscience, 18 (6), 800-6 PMID: 26007213

Rapoport M, Dawson HN, Binder LI, Vitek MP, & Ferreira A (2002). Tau is essential to beta -amyloid-induced neurotoxicity. Proceedings of the National Academy of Sciences of the United States of America, 99 (9), 6364-9 PMID: 11959919

Reitz C, & Mayeux R (2014). Alzheimer disease: epidemiology, diagnostic criteria, risk factors and biomarkers. Biochemical pharmacology, 88 (4), 640-51 PMID: 24398425

Verghese PB, Castellano JM, & Holtzman DM (2011). Apolipoprotein E in Alzheimer’s disease and other neurological disorders. The Lancet. Neurology, 10 (3), 241-52 PMID: 21349439

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Sex Bias In Autism Spectrum Disorders – Is It Real? http://brainblogger.com/2015/06/29/sex-bias-in-autism-spectrum-disorders-is-it-real/ http://brainblogger.com/2015/06/29/sex-bias-in-autism-spectrum-disorders-is-it-real/#comments Mon, 29 Jun 2015 14:00:53 +0000 http://brainblogger.com/?p=19861 An intriguing observation in the epidemiology of autism is the marked sex bias in its prevalence, with a commonly reported ratio of five males to one female. Age of diagnosis also differs between males and females, being on average later in the latter. Despite the consistent documentation of such a difference, there is a surprisingly low amount of research on sex differences in ASD.

The first question that arises in regard to this sex bias in autism spectrum disorders (ASD) is if males are indeed more prone to developing autism, or if it is due to different behavioral characteristics (real or stereotyped) between females and males.

Differences in neuroanatomy

A different neuroanatomy of the disease in males and females has actually been proposed, with some neuroanatomical sex differences in adult ASD patients having been described.

It has also been reported that brain areas which typically differ between sexes in control individuals are atypical in females, but not males with autism, suggesting what has been dubbed as neural ‘masculinization’. There is actually a theory of autism, the ‘extreme male brain’ theory, which proposes that autism represents an amplification of certain aspects of typical sexual specificities in cognition, but it has been widely criticized for being heavily based on stereotypes. Also, these proposed neuroanatomical differences raise the question of how they can underlie similar cognitive outcomes in males and females with autism.

Indeed, a study examining sex differences in developmental functioning and early social communication in children with ASD did not find any significant effects of sex, suggesting a similar phenotype in males and females, at least early in development. Another study has shown that, although no sex differences in autistic symptoms could be found, females tended to be somewhat more functional, suggesting a sex difference in the adaptive behavior. Although this was an observation from diagnosed patients, one can wonder if functional adaptations in females may mask the development of autistic traits and thereby delay or even hinder their diagnosis. This could account, at least partially, to the reported sex differences in ASD prevalence.

Differences in diagnosis

Given similar patterns of autistic traits, males are more easily diagnosed with autism than females, who usually require more coexisting features to be diagnosed with ASD. It has been argued that this may reflect a gender-bias in the diagnosis of ASD due to stereotyped views of “typical female behavior”.

For example, a young boy lacking social skills will trigger suspicion more promptly that a young girl with the same behavioral patterns, who will more likely be regarded as “just being shy”. Nevertheless, it is possible that autistic traits do develop later in females due to yet unknown different pathophysiological mechanisms.

When trying to understand the neurobiological and genetic aspects of autism in males and females, it is important to determine if the behavioral criteria for autism are appropriate for both. It has therefore been proposed that the threshold for the level of autistic traits for an individual to be considered as having ASD should be sex/gender specific. But this is a challenging question since there are too many behavioral stereotypes associated with gender that hamper these definitions.

Therefore, the answer to this question is not straightforward. The fact that the higher prevalence of ASD in males has led to a preference for males when choosing participants for research studies does not make it easier. As a result, females with autism have been somewhat neglected, and have been assumed to have the same neurobiological mechanisms as males with autism, which may not be true and may have generated a male-biased understanding of autism.

References

Hiller RM, Young RL, & Weber N (2015). Sex differences in pre-diagnosis concerns for children later diagnosed with autism spectrum disorder. Autism : the international journal of research and practice PMID: 25717130

Lai MC, Lombardo MV, Auyeung B, Chakrabarti B, & Baron-Cohen S (2015). Sex/gender differences and autism: setting the scene for future research. Journal of the American Academy of Child and Adolescent Psychiatry, 54 (1), 11-24 PMID: 25524786

Lai MC, Lombardo MV, Suckling J, Ruigrok AN, Chakrabarti B, Ecker C, Deoni SC, Craig MC, Murphy DG, Bullmore ET, MRC AIMS Consortium, & Baron-Cohen S (2013). Biological sex affects the neurobiology of autism. Brain : a journal of neurology, 136 (Pt 9), 2799-815 PMID: 23935125

Mandic-Maravic V, Pejovic-Milovancevic M, Mitkovic-Voncina M, Kostic M, Aleksic-Hil O, Radosavljev-Kircanski J, Mincic T, & Lecic-Tosevski D (2015). Sex differences in autism spectrum disorders: does sex moderate the pathway from clinical symptoms to adaptive behavior? Scientific reports, 5 PMID: 25988942

Reinhardt VP, Wetherby AM, Schatschneider C, & Lord C (2015). Examination of sex differences in a large sample of young children with autism spectrum disorder and typical development. Journal of autism and developmental disorders, 45 (3), 697-706 PMID: 25189824

Image via Dubova> / Shutterstock.

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Neuronal Transplantation May Restore Brain Functionality http://brainblogger.com/2015/06/28/neuronal-transplantation-may-restore-brain-functionality/ http://brainblogger.com/2015/06/28/neuronal-transplantation-may-restore-brain-functionality/#comments Sun, 28 Jun 2015 14:00:18 +0000 http://brainblogger.com/?p=19885 Artificial limbs let receivers lead more productive and fulfilling lives. Organ transplantations give new life to people. Science has advanced so far that it can even tinker with the workings of the brain to explore ways in which lost brain functions can be revived. Experiments are already underway to determine if neuronal transplantation can replace and restore the functionality of lost or damaged neurons.

Experiments conducted on laboratory mice provide a glimmer of hope. For instance, in a recent experiment, embryonic neurons were transplanted into the visual cortex of vision-impaired mice. These animals began to see a few weeks after the transplantation!

The findings of experiments like this one are exciting and have already led scientists to wonder if neuronal transplantation holds the key to curing brain disorders and cognitive, motor, and sensory impairment.

Neuronal transplantation and plasticity of the human brain

The term “plasticity” refers to the ability of the neuronal pathways and synaptic connections to change in response to novel experiences. It was once believed that the neural pathways and connections in the brain became fixed after an individual reaches a certain age. Not only laymen but also scientists in some quarters believed that only a child’s brain can shape and reshape itself in response to events and experiences. But the above-mentioned experiment on mice turns this idea right on its head.

Scientists have been carrying out experiments on neuronal transplantation over the past decade or so. One study points to the immense significance of stem cells in aiding neural regeneration after transplantation. Stem cells are primitive cells that can not only regenerate but also develop and differentiate into other types of cells with various functionalities.

In humans, it is believed that embryonic stem cells (ESCs) can be transplanted to reverse the effects of diseases, aging, developmental defects, and other types of tissue damage.

Neuronal transplantation: how did the mice get their sight back?

In a landmark experiment, embryonic neurons with GABA were injected into the visual cortex regions of adult laboratory mice with visual impairment. The neurotransmitter GABA is instrumental in controlling vision and several motor and cortical functions in organisms.

Several weeks after the transplantation, the mice were tested for their visual capabilities. It was found that those who were injected with the neurons not only displayed normal visual clarity but also younger and more flexible brains. It is evident from this experiment that the implanted neurons integrated seamlessly into the GABA-deficient region of the mice brain. What is interesting to note is that after transplantation, the neurons migrated to the appropriate cortical regions of the tissue associated with visual acuity, metamorphosed, and took over the characteristics and functionalities of the lost or damaged cells that were associated with vision.

Scientists are excited at another finding from this experiment. They have discovered that the transplantation of the neurons set into motion a critical period of neural development in the mice. “Critical period” refers to a time period when there is maximum plasticity of the brain. Usually this period occurs in childhood. But this experiment shows that the critical period can also be induced in adulthood. In this experiment, the implantation of the neurons created a new “critical period” that corresponded to the time after the transplantation that the neurons took to integrate into the visual cortical system of the mice and acquire the characteristics of the relevant cells.

The results indicate that neural plasticity in adult human brains may also not be fixed and that they can change under the influence of chemical and physical factors. This revolutionary experiment has got scientists excited about the self-renewal and self-generation possibilities of the human “plastic” brain.

Neuronal transplantation as a cure for brain disorders

Researchers have long been wondering if neuronal transplantation can stem the advance of and/or reverse the effects of progressive neurodegenerative diseases like Parkinson’s disease (PD), Huntington’s disease (HD), and schizophrenia. The scientists feel hopeful because diseases like PD are triggered by dysfunctional neuronal pathways or when there is loss of or damage to the neurons that hamper their ability to function normally.

PD is caused by a progressive loss of dopamine neurons in a specific part of the brain. Dopamine therapy is a standard treatment procedure for PD. According to the experimental findings reported in one study carried out on laboratory mice, fetal cells transplanted into the dopamine-deficient region of the brain can develop as fully-functional dopamine neurons to replace the lost or damaged cells and take on their functionalities. This can restore lost cerebral function and reduce the symptoms of PD in an animal case study.

Scientists have also carried out experiments to test the feasibility of this therapeutic approach on individuals afflicted with HD. In one experiment, two people with moderate HD were transplanted with fetal cells from the pre-basal ganglia region. These embryonic cells survived in the new environment and differentiated into the intended type of cell. But six years after the implantation, it was found that though the symptoms of the disease did not progress in the individuals, they were not cured either. Incidentally, the two patients who took part in the experiment survived 74 months and 79 months respectively after the transplantation.

Scientists have achieved some degree of success with neuronal transplantation in case of PD. On the other hand, the partial setback in the experiment on people suffering from HD indicates that they should continue to explore more sophisticated techniques of neuronal implantation and find out about the other factors (internal or external) that contribute to the success of the transplantation or the various developmental factors that trigger the creation of a critical period.

The limited amount of laboratory success of the neuronal transplantation procedure should not discourage scientists from searching for answers to the above problems. People are already hinging their hopes on this flicker of hope that the experiment to bring back vision in laboratory mice has brought them.

References

Davis, M., Figueroa Velez, D., Guevarra, R., Yang, M., Habeeb, M., Carathedathu, M., & Gandhi, S. (2015). Inhibitory Neuron Transplantation into Adult Visual Cortex Creates a New Critical Period that Rescues Impaired Vision Neuron, 86 (4), 1055-1066 DOI: 10.1016/j.neuron.2015.03.062

Frank, S., & Biglan, K. (2007). Long-term fetal cell transplant in Huntington disease: Stayin’ alive Neurology, 68 (24), 2055-2056 DOI: 10.1212/01.wnl.0000267703.35634.e1

Keene, C., Sonnen, J., Swanson, P., Kopyov, O., Leverenz, J., Bird, T., & Montine, T. (2007). Neural transplantation in Huntington disease: Long-term grafts in two patients Neurology, 68 (24), 2093-2098 DOI: 10.1212/01.wnl.0000264504.14301.f5

Nguyen, J. et al. (2009). Neuronal Transplantation: A Review. Practical Handbook of Neurosurgery p.1574-1584.

Sowden, J. (2014). Chapter 4 – Restoring Vision to the Blind: Stem Cells and Transplantation Translational Vision Science & Technology, 3 (7) DOI: 10.1167/tvst.3.7.6

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The Role of Serotonin and Glutamine in Aggression http://brainblogger.com/2015/06/20/the-role-of-serotonin-and-glutamine-in-aggression/ http://brainblogger.com/2015/06/20/the-role-of-serotonin-and-glutamine-in-aggression/#comments Sat, 20 Jun 2015 14:00:33 +0000 http://brainblogger.com/?p=19812 A few years ago, a quote by the Dalai Lama went viral. According to the Tibetan spiritual leader, if every kid in the world is taught to meditate starting today, the world will be able to wipe out violence in one generation. It is not surprising why this saying got liked, clicked, tweeted, shared, and commented on millions of times. With mindless violence escalating by the day, most amongst us are trying to find answers within ourselves and from around us.

Scientists too, are on the hunt to find what causes some people to be aggressive. Some in the scientific community believe that aggression has neurological roots. In particular, scientists implicate the neurotransmitters serotonin and glutamine.

Serotonin: The happy hormone and its role in tempering aggression

Several studies have proved that neurotransmitters can heavily influence behavioral traits in individuals. In particular, imbalances in the levels of neurotransmitters can trigger impulsive negative behaviors. So it is no surprise that scientists are now toying with the idea that neurotransmitters may have a role to play in raising or lowering aggression levels in individuals.

They are particularly interested in the role of serotonin, the “happy hormone” that is known to influence our moods, anxiety levels, impulse-control abilities, and thinking powers. When present in optimal amounts in the body, this substance gives us loads of positive energy and will power.

Researchers believe that just as the right level of serotonin keeps us sunny and cheerful, its imbalance can trigger negative emotions and disruptive behavior. There have been several studies to investigate the role of serotonin imbalance in triggering impulsive aggressive behavior. According to one study, serotonin deficiency or inadequate functioning of the neurotransmitter can make a person impulsively aggressive. Scientists believe that serotonergic dysfunction also makes the dopamine system go awry. These dual developments can trigger co-morbid psychotic disorders that, in turn, make the individual more prone to aggression.

Another study points to the link between certain variations in the serotonin transporter (5-HTT) gene and persistent, pervasive aggression in children. These variations cause the serotonin system to dysfunction triggering aggressive behavior in the child. According to the scientists who conducted this study, children who display persistently aggressive behavior tend to develop anti-social tendencies when they grow up. Impulsive aggression is a common manifestation of anti-social behavioral trends.

Glutamine and aggression

Glutamic acid is an amino acid that is converted to glutamine. Glutamine also gets reconverted to glutamic acid. Glutamic acid is also a precursor to GABA, a critical neurotransmitter that plays an integral role in regulating emotions.

The glutamate neurotransmitter helps support the central nervous system. The proper functioning of this transmitter is critical to keep away depression, enhance mood, and increase mental alertness. A recent study, however, suggests that glutamate may also have a role to play in triggering aggressive behavior in individuals.

In this study conducted on laboratory mice, it was found that injecting glutamate in the brains of the animals raised their levels of aggression towards other mice when provoked. The degree of aggression displayed was proportional to the dosage of the glutamate. What is more, scientists also discovered that the mice brains released more glutamate when they displayed aggressive behavior.

The results may not seem very surprising because excess glutamate in the body has been positively linked to anxiety, mood swings, hyperactivity, and confusion that may trigger aggression in some individuals.

In another study carried out on two groups of children, one with autism and the other healthy, it was discovered that the autistic children had higher levels of glutamate but decreased glutamine in their systems compared to their healthier peers. These were the two most significant genetic-level differences between the autistic and healthy children.

Aggression is a common characteristic of autism. The above findings have prompted researchers to explore clinical treatment methods that target the levels of glutamate and glutamine to control aggression in autistic children.

Aggression and mental isorders

Persistent and pervasive aggressive tendencies that have genetic roots increase the chances of individuals developing co-morbid mental disorders like schizophrenia and depression. Abnormal functioning of the glutamate/GABA-glutamine cycle can trigger mental disorders by hampering the normal neural signaling process.

GABA is a neurotransmitter that acts as a sort of natural tranquilizer in the brain. It lulls activity in the limbic system that is responsible for triggering emotions like anxiety and panic. Mental disorders can occur when the glutamate/GABA ratio gets skewed. Because aggression may also be triggered by an imbalance in the glutamate/GABA-glutamine cycle, aggression control is critical to reduce the chances of an individual developing mental illness.

Genetically-induced aggression points to neurotransmitter deficiencies. Neurotransmitter deficiencies can also manifest in other ways like an individual developing behavioral disorders, ADHD, and chronic and debilitating stress and anxiety. So it is imperative that researchers try to understand the roots of aggression to gain greater insights into several other mental diseases.

Aggression has its roots in several different neural regions. The various neurotransmitters interact with one another in diverse ways to trigger, exaggerate, or temper aggressive tendencies in individuals. However, the role of serotonin and glutamine seems to be more critical than others.

The above-mentioned findings on the role of serotonin and glutamine in triggering impulsive aggressive behavior present promising avenues for finding ways to manage aggression in individuals. Successful clinical and therapeutic intervention (like administering drugs, or deep brain stimulation) will have positive repercussions for diverse groups of people.

Autistic children can develop greater social skills. Criminal offenders may get a shot at reclaiming their lives by learning to manage their aggressive natures. Many other men and women can hope they can curb their aggressive streaks and lead more peaceful and productive personal and professional lives. Knowing more about the neurobiological roots of aggression and aggression control can help many people gain back control of their lives, relationships, and careers.

References

Beitchman, J., Baldassarra, L., Mik, H., De Luca, V., King, N., Bender, D., Ehtesham, S., & Kennedy, J. (2006). Serotonin Transporter Polymorphisms and Persistent, Pervasive Childhood Aggression American Journal of Psychiatry, 163 (6), 1103-1105 DOI: 10.1176/ajp.2006.163.6.1103

Ghanizadeh, A. (2013). Increased Glutamate and Homocysteine and Decreased Glutamine Levels in Autism: A Review and Strategies for Future Studies of Amino Acids in Autism Disease Markers, 35, 281-286 DOI: 10.1155/2013/536521

Love, T., Stohler, C., & Zubieta, J. (2009). Positron Emission Tomography Measures of Endogenous Opioid Neurotransmission and Impulsiveness Traits in Humans Archives of General Psychiatry, 66 (10) DOI: 10.1001/archgenpsychiatry.2009.134

Morrison TR, & Melloni RH Jr (2014). The role of serotonin, vasopressin, and serotonin/vasopressin interactions in aggressive behavior. Current topics in behavioral neurosciences, 17, 189-228 PMID: 24496652

Seo, D., Patrick, C., & Kennealy, P. (2008). Role of serotonin and dopamine system interactions in the neurobiology of impulsive aggression and its comorbidity with other clinical disorders Aggression and Violent Behavior, 13 (5), 383-395 DOI: 10.1016/j.avb.2008.06.003

Takahashi, A., Lee, R., Iwasato, T., Itohara, S., Arima, H., Bettler, B., Miczek, K., & Koide, T. (2015). Glutamate Input in the Dorsal Raphe Nucleus As a Determinant of Escalated Aggression in Male Mice Journal of Neuroscience, 35 (16), 6452-6463 DOI: 10.1523/JNEUROSCI.2450-14.2015

Zhao, C., & Gammie, S. (2014). Glutamate, GABA, and glutamine are synchronously upregulated in the mouse lateral septum during the postpartum period Brain Research, 1591, 53-62 DOI: 10.1016/j.brainres.2014.10.023

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Best and Worst of Neuroscience and Neurology – May 2015 http://brainblogger.com/2015/06/18/best-and-worst-of-neuroscience-and-neurology-may-2015/ http://brainblogger.com/2015/06/18/best-and-worst-of-neuroscience-and-neurology-may-2015/#comments Thu, 18 Jun 2015 14:00:32 +0000 http://brainblogger.com/?p=19883 The month of May saw many interesting developments, both in fundamental neuroscience and neurology and in practical aspects of dealing with brain-related diseases and disorders. The selection below outlines some of my favorite publications.

On May 28, the scientific community marked the birthday of Stanley Prusiner, the receiver of the 1997 Nobel Prize in Medicine and Physiology. Back in 1982, Dr Prusiner, who now heads the Institute for Neurodegenerative Diseases at UCSF, discovered and described prions, a new class of infectious agents composed exclusively of self-replicating protein.

Initially viewed mostly as a scientific curiosity, prions turned out to play key role in the development and progression of neurodegenerative diseases such as Alzheimer’s disease, Huntington’s disease, Parkinsonism and mad cow disease. Clear understanding of the role prions are playing in the mechanisms of these diseases gives, for the first time, a real hope of finding drugs to manage and treat these conditions.

THE BEST

Another twist in the Alzheimer’s story

In recent years, the science of neurodegenerative disorders has witnessed quite a few unexpected discoveries. Yet another twist in the studies of Alzheimer’s disease was revealed in the latest issue of Brain journal. It was always assumed that the onset of the disease is caused by the overproduction of certain toxic peptides. Novel data demonstrate, however, that it is the deficiency in the removal of toxic products, amyloid-beta specifically, rather than their increased production, which is causing the first clinical signs of the disease. This information will help in developing more specific targeting pharmaceutical approaches for prevention and slowing down the onset of the symptoms in the patients at risk.

New biomaterial helps in neuronal transplantation

Without doubt, the brain is the most complex organ of human body. No wonder we still have very few approaches to treat brain disorders and injuries. But progress does take place. Stem cell transplantation is viewed by many people as a highly promising technique that can help in treating various disorders and injuries, including brain damage. There are, however, several major technical issues that should be addressed before stem cell transplantation can actually succeed. Stem cells are not particularly easy to integrate into a tissue, and there is a challenge in keeping them alive at a new place.

This month, Canadian scientists have reported very promising results from their experiments with “hydrogel”, a new material that keeps transplanted stem cells bound together and boosts their healing properties. In experiments on rats, the researchers demonstrated that the use of hydrogel helps to partially reverse blindness and help in recovery from stroke. Hydrogel certainly looks like a very promising biomaterial for therapies aimed to repair nerve damage.

Obese teens easily targeted by junk food adverts

Rather unexpected findings were published this month in the journal Cerebral Cortex. We are all aware that TV commercials can be quite persuasive, but it appears that junk food adverts have particularly high appeal to obese teenagers.

By monitoring the brain activity of participants watching TV programs that included various advertisements, the scientists found that junk food adverts directly, and disproportionally, activate the regions of the brain controlling pleasure and taste in these groups. The findings point to a potential mechanism behind the formation of unhealthy eating habits.

Having a bigger brain IS a survival benefit

Evolutionary biologists always assumed that bigger brain size is associated with more adaptable behaviour and thus brings survival benefits to a species. As it turns out, this concept was never actually tested experimentally.

Scientists from Austria have helped to fill this knowledge gap in a relatively simple but revealing experiment with guppy fish. They selected two groups of fish with brains differing in size by 12% and then released them in a semi-natural stream with predators, pike cichlids. Half a year later, significantly more large-brained female guppy fish survived compared with their smaller-brained counterparts. Surprisingly, larger-brained males did not show better survival rate. Researchers believe that this difference was caused by the fact that the males of this species are very brightly coloured and thus are more easily spotted by predators.

Seeing without eyes?

Another fascinating finding came from the field of zoology this month. Scientists studying the ability of octopi skin to change color found that the skin of these animals is also sensitive to light. It contains opsins, the same light-sensitive chemicals that are found in eyes. Although the octopus cannot make the picture of its surroundings by the skin alone, it certainly can sense the brightness of the light and its changes. Unusually, this sensing and the consequent skin response occur without the input of nervous system in the processing of information.

THE WORST

Scientific theories and hypotheses often turn out to be wrong. There is a lot to learn from mistakes.

DNA of neurons constantly gets re-written

We always believed that the genes we inherit from our parents are fixed and unchangeable for life. Well, this is not exactly correct. Genes, and their activity, can be substantially modulated via methylation, a form of chemical modification, of DNA bases.

New data suggest that this DNA modifying activity is particularly intense in neurons, higher than anywhere else in the body. Changes in DNA methylation level influences the activity of certain genes and leads to changes in the level of activity of neurons, particularly when it comes to inter-neuronal signalling and communication. The process appears to be crucial for the normal brain functioning. Scientists also believe that problems with this DNA “re-writing” process may be linked to some brain disorders.

DNA methylation and drug addiction

Molecular mechanisms behind drug addiction have been the focus of intense research for many years, but it appears that new data published this month may point to a major flaw in our understanding of the problem. These new findings also deal with the methylation of genes in brain cells.

Researchers studying cocaine addiction in rat models found that the drug withdrawal symptoms are linked to the epigenetic changes in DNA. Specifically, certain genes get methylated following drug withdrawal, and these changes become particularly pronounced only after a long period (a month) without the drug. Apparently, the addicted personality is formed not during the drug use, but upon quitting. Providing rats with methylation inhibitors after long period without the drug substantially reduced the drug seeking behaviour. If these findings are proven correct for humans, a major review of strategies for treating drug addiction will be needed. In the view of novel data, the current treatment approaches appear to worsen withdrawal symptoms rather than help fight the addiction effectively.

Brain connectivity influences success in quitting smoking

Smokers demonstrate all the classical symptoms of drug addiction. Despite the availability of various aids to quit smoking, leaving the habit behind appears to be remarkably hard for many people. New findings suggest that people who do succeed might have rather specific brain connections that help them to overcome addiction. Brain MRI studies show that successful quitters have better synchrony between the insula and the somatosensory cortex. The former part of the brain is responsible for cravings while the latter one coordinates our senses of touch and motor control. The findings indicate that traditional approaches often fail simply because they do not address the key issue of brain connectivity.

Two other articles published this month question some of our long-held views on brain functions.

Brain actively transports essential fats

The brain contains lots of fats critical to its function. It was always believed that these fats are produced by the brain cells themselves. However, two articles published this month in Nature Genetics prove this wrong. Researchers have demonstrated that blood-circulating lysophosphatidylcholines (LPCs) composed of essential fatty acids like omega-3 get actively transported into the brain cells. Various brain abnormalities like intellectual disabilities and microcephaly can be developed when these transportation mechanisms are affected. The findings might help to pave the way for better targeting brain nutrition, particularly in babies, mothers, and elderly individuals at risk of neurodegenerative disorders.

Oxytocin: not as lovely as it seems

Oxytocin is often praised as a love hormone responsible for maternal, romantic and social bonding. However, more probing investigations with the use of intranasal oxytocin administration show some interesting similarities between the effect of oxytocin and alcohol. Like alcohol, oxytocin can affect our sense of fear and make us to take rather risky actions which would normally avoided. This darker side of the “love hormone” needs to be further studied.

References

Addicott, M., Sweitzer, M., Froeliger, B., Rose, J., & McClernon, F. (2015). Increased Functional Connectivity in an Insula-Based Network is Associated with Improved Smoking Cessation Outcomes Neuropsychopharmacology DOI: 10.1038/npp.2015.114

Alakbarzade, V., Hameed, A., Quek, D., Chioza, B., Baple, E., Cazenave-Gassiot, A., Nguyen, L., Wenk, M., Ahmad, A., Sreekantan-Nair, A., Weedon, M., Rich, P., Patton, M., Warner, T., Silver, D., & Crosby, A. (2015). A partially inactivating mutation in the sodium-dependent lysophosphatidylcholine transporter MFSD2A causes a non-lethal microcephaly syndrome Nature Genetics DOI: 10.1038/ng.3313

Ballios, B., Cooke, M., Donaldson, L., Coles, B., Morshead, C., van der Kooy, D., & Shoichet, M. (2015). A Hyaluronan-Based Injectable Hydrogel Improves the Survival and Integration of Stem Cell Progeny following Transplantation Stem Cell Reports, 4 (6), 1031-1045 DOI: 10.1016/j.stemcr.2015.04.008

Guemez-Gamboa, A., Nguyen, L., Yang, H., Zaki, M., Kara, M., Ben-Omran, T., Akizu, N., Rosti, R., Rosti, B., Scott, E., Schroth, J., Copeland, B., Vaux, K., Cazenave-Gassiot, A., Quek, D., Wong, B., Tan, B., Wenk, M., Gunel, M., Gabriel, S., Chi, N., Silver, D., & Gleeson, J. (2015). Inactivating mutations in MFSD2A, required for omega-3 fatty acid transport in brain, cause a lethal microcephaly syndrome Nature Genetics DOI: 10.1038/ng.3311

Kotrschal, A., Buechel, S., Zala, S., Corral, A., Penn, D., & Kolm, N. (2015). Brain size affects female but not male survival under predation threat Ecology Letters DOI: 10.1111/ele.12441

Krohn, M., Bracke, A., Avchalumov, Y., Schumacher, T., Hofrichter, J., Paarmann, K., Frohlich, C., Lange, C., Bruning, T., von Bohlen und Halbach, O., & Pahnke, J. (2015). Accumulation of murine amyloid-  mimics early Alzheimer’s disease Brain DOI: 10.1093/brain/awv137

Massart, R., Barnea, R., Dikshtein, Y., Suderman, M., Meir, O., Hallett, M., Kennedy, P., Nestler, E., Szyf, M., & Yadid, G. (2015). Role of DNA Methylation in the Nucleus Accumbens in Incubation of Cocaine Craving Journal of Neuroscience, 35 (21), 8042-8058 DOI: 10.1523/JNEUROSCI.3053-14.2015

Mitchell, I., Gillespie, S., & Abu-Akel, A. (2015). Similar effects of intranasal oxytocin administration and acute alcohol consumption on socio-cognitions, emotions and behaviour: Implications for the mechanisms of action Neuroscience & Biobehavioral Reviews, 55, 98-106 DOI: 10.1016/j.neubiorev.2015.04.018

Ramirez, M., & Oakley, T. (2015). Eye-independent, light-activated chromatophore expansion (LACE) and expression of phototransduction genes in the skin of Octopus bimaculoides Journal of Experimental Biology, 218 (10), 1513-1520 DOI: 10.1242/jeb.110908

Rapuano, K., Huckins, J., Sargent, J., Heatherton, T., & Kelley, W. (2015). Individual Differences in Reward and Somatosensory-Motor Brain Regions Correlate with Adiposity in Adolescents Cerebral Cortex DOI: 10.1093/cercor/bhv097

Yu, H., Su, Y., Shin, J., Zhong, C., Guo, J., Weng, Y., Gao, F., Geschwind, D., Coppola, G., Ming, G., & Song, H. (2015). Tet3 regulates synaptic transmission and homeostatic plasticity via DNA oxidation and repair Nature Neuroscience, 18 (6), 836-843 DOI: 10.1038/nn.4008

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Is Your Brain Male or Female? http://brainblogger.com/2015/06/06/is-your-brain-male-or-female/ http://brainblogger.com/2015/06/06/is-your-brain-male-or-female/#comments Sat, 06 Jun 2015 14:00:36 +0000 http://brainblogger.com/?p=19682 In his book The Essential Difference: Male And Female Brains And The Truth About Autism, Simon Baron-Cohen opens with a phrase capable of causing infinite controversy: “The female brain is predominantly hard-wired for empathy. The male brain is hard-wired for understanding and building systems.”

When I first became interested in gender differentation in the brain, after reading about prairie voles and how oxytocin made them more nurturing as parents (in Steven Johnson´s book Mind Wide Open), I started commenting on new findings about the female brain with friends and acquaintances. The response I got was usually rather skeptical. This was especially the case when I tried to bring the subject up with women.

Apparently, after fighting for equal rights for centuries, many women were reluctant to acknowledge significant differences between the male and female brain. The popularization of neuroscience, aided by advances in the research, have conquered only a fraction of that skepticism. But the truth is that none of it is justified.

Vasopressin and Empathy

Structural differences between the male and female brain, most prominently connectivity between the hemispheres, are well known, while many aspects about the way each one of them works are still a mystery.

A recent study focusing on the synthesis of neuropeptides vasopressin (VP) and oxytocin (OT), which are involved in a large number of social behaviors including mate bonding and parental care, concluded that VP and OT systems frequently mediate sex differences in such behaviors.

Another study from earlier this year found that intranasal VP, yet not oxytocin, altered empathic behavior in both men and women. VP systems in male and female brains have shown many differences across different species of rodents, yet the way these differences affect VP release in the brain is still unknown. At any rate, in spite all the uncharted territory, it would seem that when Baron-Cohen attributed empathy to females, he was not too far from the truth.

Creativity in the Male and Female Brain

One of the things scientists observe most frequently when doing fMRIs of the female and male brain executing the same activities is that different areas of the brain tend to “light up.” While one sex seldom outperforms the other, the way men and women solve a problem, recall certain types of memories, or engage in creative processes appears to be quite different.

During a study focusing on creative processes, such as creative conceptual expansion and general divergent thinking, men and women showed indistinguishable performance levels across the different tasks proposed. However, fMRIs revealed profound strategic differences between the genders. For example, while in men, brain areas related to semantic cognition, rule learning, and decision making were primarily engaged during conceptual expansion, in women there was higher activity in regions associated with speech processing and social perception.

Oxytocin and Parenting

More popular than differences in empathic behavior and creativity strategies, oxytocin is the unquestioned star when it comes to making a name for itself in pop culture. Oxytocin is connected with nurturing and caring behaviors towards offspring. Research has shown that besides playing a key role in childbirth and early mother-child bonding, oxytocin release, alongside dopamine release, may also result from rewarding interactions with infants. It has actually been observed that fathers who spend time with their kids may stimulate the oxytocin-dopamine reward system in their brains.

In fact, evidence points to the possibility to “rewire” the male brain to accommodate parenting styles similar to those associated with females. For example, in one study, a vole from a species that is not nurturing with offspring was placed among a group of nurturing voles. The result was that regardless of its neurological predisposition to be less nurturing, the vole learnt from the individuals around it and became a nurturing parent.

When Babies Cry

The question is, if males can acquire characteristics associated with the female brain, why is gender differentiation in the brain still such a big deal?

Well, there is still more functional differentiation to go. Several studies have analyzed the reactions of both mothers and fathers to the crying of their infants. Scans have revealed a greater activation of amygdala and basal ganglia in brand new mothers compared with fathers, which is consistent with mothers being more preoccupied than fathers in these circumstances. Responses to baby stimuli have also been linked to OT pathways, as mothers who give birth through vaginal birth, which stimulates oxytocin release, show greater brain activity in response to the cries of their own babies versus other babies.

Arguably, parenting styles and how they originate in brain function may be the most salient aspect of male-female differentiation in the brain. However, much of the evidence in these respect points to fathers simply being slower learners. For example, when it comes to baby cry stimuli, it may take fathers between 6 to 18 months to match the level of brain activation shown by mothers, but they eventually get there.

The Extreme Male Brain

With as many champions as detractors, Baron-Cohen is still a top expert in the field. His theory of the extreme male brain may be the culprit of the passions his work never fails to excite. Basically, he proposes that the autistic brain is the “full-on” male brain, namely, zero empathy, all systemization.

In a study published earlier this year, Baron-Cohen and his colleagues presented new evidence for the extreme male brain theory in the shape of hemodynamic response measurements during second-order false-belief task and coherent story task performances. Since the measurements revealed “sex difference in the neural basis of Theory of Mind (a cognitive component of empathy) and pragmatic language,” the researchers concluded that this was in line with the extreme male brain hypothesis; a conclusion that seems slightly far-fetched. While the findings do not disprove the extreme male brain theory, they seem to contribute not much more than a grain of sand in the building of a giant castle.

What About the Gay Brain?

An interesting question that surfaces whenever the male and female brain are discussed is what happens with the gay brain? In other words, do homosexual women have a brain more akin to men´s and vice versa?

A research team tried to answer this question by studying functional cerebral lateralization for the processing of facial emotions. The sample comprised 30 heterosexual males, 30 heterosexual females and 40 gay males. Results revealed that while men were right-lateralized when viewing female faces, homosexual men were as left-lateralized as women during the same activity. Thus, researchers concluded that “gay men are feminized in some aspects of functional cerebral lateralization for facial emotion.”

Perhaps the future of male-female brain differentiations studies lies in the understanding of brain formation and development. A study from Beijing University, which appeared in Acta Radiologica earlier this year, attempts to draw conclusions from studying the brains of 400 young adults. The authors observed significant topographical differences between the sexes, including gray matter volume and cortical thickness, both larger in females, and posed a question neuroscientists will bust their own brains – whether male or female – trying to answer in the years to come: Does the difference in the topological architecture represent underlying behavioral and cognitive differences between genders?

As with many areas of neuroscience, when it comes to gender differentiation in the brain, experts today seem to have many more questions than answers, but this is precisely what makes the field so exciting.

Meanwhile, common people continue to devour books about the male and the female brain, in the hopes of understanding the other sex better, a pursuit as likely to be crowned with success anytime soon as the full understanding of the brain itself.

References

Abraham A, Thybusch K, Pieritz K, & Hermann C (2014). Gender differences in creative thinking: behavioral and fMRI findings. Brain imaging and behavior, 8 (1), 39-51 PMID: 23807175

Dumais KM, & Veenema AH (2015). Vasopressin and oxytocin receptor systems in the brain: Sex differences and sex-specific regulation of social behavior. Frontiers in neuroendocrinology PMID: 25951955

Frank CK, Baron-Cohen S, & Ganzel BL (2015). Sex differences in the neural basis of false-belief and pragmatic language comprehension. NeuroImage, 105, 300-11 PMID: 25264229

Hu Y, Xu Q, Shen J, Li K, Zhu H, Zhang Z, & Lu G (2015). Small-worldness and gender differences of large scale brain metabolic covariance networks in young adults: a FDG PET study of 400 subjects. Acta radiologica (Stockholm, Sweden : 1987), 56 (2), 204-13 PMID: 24763919

Nakstad, P. (2015). Gender differences in the human brain Acta Radiologica, 56 (2), 131-132 DOI: 10.1177/0284185114562993

Rahman Q, & Yusuf S (2015). Lateralization for Processing Facial Emotions in Gay Men, Heterosexual Men, and Heterosexual Women. Archives of sexual behavior PMID: 25564038

Swain, J., Kim, P., Spicer, J., Ho, S., Dayton, C., Elmadih, A., & Abel, K. (2014). Approaching the biology of human parental attachment: Brain imaging, oxytocin and coordinated assessments of mothers and fathers Brain Research, 1580, 78-101 DOI: 10.1016/j.brainres.2014.03.007

Image via Andrey Arkusha / Shutterstock.

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The Multiple Faces of “Love Hormone” Oxytocin http://brainblogger.com/2015/06/04/the-multiple-faces-of-love-hormone-oxytocin/ http://brainblogger.com/2015/06/04/the-multiple-faces-of-love-hormone-oxytocin/#comments Thu, 04 Jun 2015 14:00:45 +0000 http://brainblogger.com/?p=19757 Oxytocin acquired the title of “love hormone” when it was discovered that it influenced parental — especially the connection between mother and child — and romantic bonding. But now researchers have discovered that it also influences social communications, the dynamics of in- and out-group relationships, and social stress. Scientists also believe that abnormal functioning of the oxytocin neural pathway may aggravate the symptoms of communications and social skills disorders associated with mental diseases like autism and schizophrenia.

New Insights into Oxytocin’s Role in Maternal Behavior

Scientists knew that oxytocin had a role to play in strengthening the bond between mother and child. But now they have found out that oxytocin also affects neural signals in the brain of the mother and influences her social responses.

In an experiment conducted on laboratory mice with pups, scientists discovered that when the little ones were separated from their mums, they produced ultrasonic SOS calls. The mother mouse picked up these signals to locate her pups. The mother mice responded similarly — started looking for their pups — when the scientists played the pup distress calls on speakers.

The scientists investigated how oxytocin is involved in this behavior.

The left auditory cortex of the brain receives the sound signals. This part of the brain has a large number of oxytocin receptors. The hormone levels increased in the mother mice when they heard the distress calls of their pups. Oxytocin not only made the mother mice respond to their pups but also inhibited her brain’s ability to process other social signals.

In the above experiment, it was also found that female mice without pups did not respond to distress calls made by pups of other mice. But when they were injected with oxytocin, they responded to the distress calls by rushing to search for and rescue the pups even though those were not their own.

This newly-discovered role of oxytocin is, however, not surprising. After all, babies are helpless and unable to defend themselves if they are separated from their mums. So it seems natural that nature intended oxytocin to exert influence on mothers in this way.

Oxytocin and Our Responses to Social Stimuli

The oxytocin system is critical to the expression of three basic social bonds — parental, filial, and romantic. According to one study, the levels of oxytocin remain more or less stable in individuals over extended periods of time and go on to play crucial role in the expression of other types of social attachment behavior later in their lives.

Scientists also believe that oxytocin interacts with neural, physical, and mental factors to develop unique expressions of social cognition and empathy in humans. For instance, scientists have discovered that the quality of early-life parental care tends to influence the way children form attachments in adulthood.

In 2005, an interesting study was conducted on two groups of children. The kids in one group were raised by their biological parents. The children in the other group were adopted, but they had been raised in orphanages where they were deprived of the typical care-giving environment that the children of the other group were raised in. The oxyotcin levels in the children from both groups were monitored when they were in contact with their mothers—biological or adopted. It was found that the children who were raised by their biological parents showed an increase in oxytocin levels while levels in the other group of children remained constant. So it is evident that early-life social experience influences the way individuals form relationships later on in their lives.

The above findings led scientists to explore the connection between oxytocin and social disorders that develop during childhood, like autism spectrum disorders. And, to their surprise, they also found out that oxytocin plays a role in managing the symptoms of certain mental illnesses like schizophrenia.

Oxytocin and Mental Illnesses

The “love hormone” oxytocin floods us with feel-good vibes. It has another beneficial face too.

According to a recent study, intranasal administration of oxytocin can improve the ability of schizophrenia patients to recognize negative emotions, like fear, in other people. It was found during the study that schizophrenia patients whose baseline performance was below median level showed greater improvement when they were administered oxytocin compared to patients who were more capable.

These findings have already unleashed a slew of research into the various aspects that need to be considered before administering oxytocin for therapeutic purposes to patients suffering from mental illnesses. For instance, one study suggests that the efficacy of intranasal administration of oxytocin is dependent on gender, hormonal and genetic profiles, and attachment history. Other scientists have investigated the effects of different doses of oxytocin on patients.

These studies are crucial for finding out how long the effects of oxytocin stays in laboratory patients because elevated levels of oxytocin can also trigger anxiety.

The Adverse Effects of Oxytocin

The “love hormone” oxytocin has been found to have a disturbing effect as well when present in more-than-normal amounts in the human body. For instance, it was shown that oxytocin also influences the memory. In an experiment conducted on laboratory mice, it was found that under conditions of social stress oxytocin fires the lateral septum region of the mouse brain, a region that intensifies memories. This means that oxytocin turns a stressful experience into a long-standing painful memory that can trigger anxiety and fear every time an individual confronts similar stressors in future. Chronic anxiety and fear can also lead to depression.

In another study, it was found that women who reported less-than-satisfactory quality of relationships with their partners and longer periods of time in their lives spent without romantic attachments had more oxytocin and the stress hormone cortisol than women who enjoyed more satisfying relationships.

These findings seem crucial considering that scientists are also toying with the idea of using oxytocin to manage the anxiety symptoms. It is evident that oxytocin is not only associated with good and happy feelings.

The discovery of new faces of oxytocin presents intriguing avenues for further study. These studies should help scientists and psychiatrists better understand and accurately analyze why we behave the way we do in specific social situations and with other human beings.

References

Feldman, R. (2012). Oxytocin and social affiliation in humans Hormones and Behavior, 61 (3), 380-391 DOI: 10.1016/j.yhbeh.2012.01.008

Fischer-Shofty, M., Shamay-Tsoory, S., & Levkovitz, Y. (2013). Characterization of the effects of oxytocin on fear recognition in patients with schizophrenia and in healthy controls Frontiers in Neuroscience, 7 DOI: 10.3389/fnins.2013.00127

Fries, A., Ziegler, T., Kurian, J., Jacoris, S., & Pollak, S. (2005). From The Cover: Early experience in humans is associated with changes in neuropeptides critical for regulating social behavior Proceedings of the National Academy of Sciences, 102 (47), 17237-17240 DOI: 10.1073/pnas.0504767102

Guzmán, Y., Tronson, N., Jovasevic, V., Sato, K., Guedea, A., Mizukami, H., Nishimori, K., & Radulovic, J. (2013). Fear-enhancing effects of septal oxytocin receptors Nature Neuroscience, 16 (9), 1185-1187 DOI: 10.1038/nn.3465

van IJzendoorn, M., Bhandari, R., van der Veen, R., Grewen, K., & Bakermans-Kranenburg, M. (2012). Elevated Salivary Levels of Oxytocin Persist More than 7?h after Intranasal Administration Frontiers in Neuroscience, 6 DOI: 10.3389/fnins.2012.00174

MacDonald, K. (2013). Sex, Receptors, and Attachment: A Review of Individual Factors Influencing Response to Oxytocin Frontiers in Neuroscience, 6 DOI: 10.3389/fnins.2012.00194

Marlin, B., Mitre, M., D’amour, J., Chao, M., & Froemke, R. (2015). Oxytocin enables maternal behaviour by balancing cortical inhibition Nature, 520 (7548), 499-504 DOI: 10.1038/nature14402

Quintana, D., Kemp, A., Alvares, G., & Guastella, A. (2013). A role for autonomic cardiac control in the effects of oxytocin on social behavior and psychiatric illness Frontiers in Neuroscience, 7 DOI: 10.3389/fnins.2013.00048

Taylor, S., Gonzaga, G., Klein, L., Hu, P., Greendale, G., & Seeman, T. (2006). Relation of Oxytocin to Psychological Stress Responses and Hypothalamic-Pituitary-Adrenocortical Axis Activity in Older Women Psychosomatic Medicine, 68 (2), 238-245 DOI: 10.1097/01.psy.0000203242.95990.74

Shalev, I., & Ebstein, R. (2013). Frontiers in oxytocin science: from basic to practice Frontiers in Neuroscience, 7 DOI: 10.3389/fnins.2013.00250

Image via Svetlana Fedoseyeva / Shutterstock.

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Flab is Fine – The Advantages of Being Overweight http://brainblogger.com/2015/05/31/flab-is-fine-the-advantages-of-being-overweight/ http://brainblogger.com/2015/05/31/flab-is-fine-the-advantages-of-being-overweight/#comments Sun, 31 May 2015 16:18:33 +0000 http://brainblogger.com/?p=19739 Yes, you read right. Flab is not always bad. Scientists have discovered that being a little overweight comes with quite a few benefits.

According to several studies, the much-maligned fat cells, the ones that many people jog, sprint, swim, and walk to melt away, boost our energy levels. These fat cells crosstalk with the brain, as was discovered in experiments on laboratory mice. Scientists also indicate that the presence of an optimum number of fat cells in the body enhances longevity and keeps away several age-related symptoms and disorders.

Fat Cells and the Brain

Although the common man continues to treat fat as bad, and fat cells as things to get rid of, scientists have been working with fat cells for several years to uncover their physiological roles and relevance. In an earlier experiment carried out on lab mice, it was found that the hormone leptin produced by fat cells carries information about the amount of energy stored in these tissues in the abdominal region to the central nervous system. Leptin, or the “satiety” hormone, stimulates the brain to trigger signals that suppress the need for taking food. So there is compelling evidence that fat cells in the body communicate with the brain and influence the latter’s actions.

Another study indicates that the hypothalamus region of the brain communicates with adipose or fat tissues and regulates various metabolic processes. According to the findings of this study, the mammalian hypothalamus houses a pacemaker of sorts that monitors and regulates various core biological processes like eating, metabolism of food, and the sleep/wake cycle. This is a 24-hour clock that also influences physical activity and energy levels in individuals.

There are several components like proteins BMAL1 and CLOCK that regulate the 24-hour clock and keep it ticking and working the way it should. BMAL1 and CLOCK are also present within fat cells. In the above-mentioned study carried out on laboratory mice, it was found that animals with mutant varieties of BMAL1 and CLOCK had wayward circadian clock rhythms. These animals also exhibited several metabolic disorders that developed when the normal functionality of the ß cells in the pancreas was hampered.

These landmark studies shed critical insights into the pathogenesis of metabolic diseases like type 2 diabetes. The findings from the above-mentioned studies also led scientists to think that having a bit of fat is not that bad, after all. Scientists believe that human beings can benefit significantly from having a body mass index that skims the lower end of the range that is usually considered to be overweight. We need fat to survive!

Fat: Its Effect on the Hypothalamus and Pancreas

According to recent studies, fat cells communicate with the hypothalamus. This region of the brain is responsible for aging, longevity, and maintaining the energy levels of the body. Additionally, the hypothalamus regulates heart rate, blood pressure, hunger, thirst, and the sleep/wake cycle.

The presence of fat cells optimized the functions of the hypothalamus leading to greater energy levels in individuals. The main player in this development is an enzyme nicotinamide phosphoribosyltransferase (NAMPT) produced by fat tissues. NAMPT is involved in production of NAD, one of the energetic substances in the cell that is responsible for maintaining optimal cellular functionality. The scientists discovered that adipose tissues typically produce large quantities of NAMPT and some of it end up in the bloodstream and gets transported to the brain.

In the course of this study, scientists discovered that when there was a lack of the NAMPT enzyme in the fat cells, there was also a considerable drop in the energy levels within the adipose tissues. Although other major organs and muscles of the body remained unaffected by the change in the levels of this enzyme, the hypothalamus exhibited a similar drop in energy levels.

There were also other developments when the amount of this enzyme dropped inside the fat cells and the hypothalamus. An increase in the energy levels of the hypothalamic cells also enhances the functionality of the SIRT1 protein. This protein has been linked to longevity in mice.

These findings should also interest people living with diabetes. Fat cells produce NAMPT, and NAMPT generates nicotinamide mononucleotide that stimulates pancreatic beta cells to churn out more insulin. Although pancreatic cells themselves produce NAMPT, the amount is not adequate. So the pancreas has to depend on the fat cells to supplement its production. So the fat cells also communicate with the pancreas to regulate the production of NAMPT.

However, researchers sound a note of warning. Obesity has been conclusively linked with the development of type 2 diabetes. It is evident that there is a limit up to which the NAMPT enzyme can go on enhancing the functionality of the pancreas. Once this limit is reached, the beneficial effects of NAMPT are negated.

It is evident that a certain amount of fat is necessary for the body to not only maintain its core physiological functions but also for its survival.

How Much Fat is Good?

The findings of the above-mentioned studies will surely interest weight-watchers, and it is natural for them to wonder how much fat is good for the body. Scientists do not yet have an exact answer to this question. They are, however, quick to warn that their findings should in no way be interpreted as a license to go on a binge-eating spree, cancel the gym membership, or stop going for the morning jog around the park. Being on either end of the underweight-morbidly obese spectrum is bad for you.

So here’s the lesson. If you were trying to lose weight, keep at it. But don’t resort to fad diets, starvation, and obsessive exercising to attain an unhealthy body weight. Being a little overweight has long-term benefits. And it is not really surprising that this phenomenon, like many other processes in the body, is linked to the way our brain functions.

References

Revollo, J., Körner, A., Mills, K., Satoh, A., Wang, T., Garten, A., Dasgupta, B., Sasaki, Y., Wolberger, C., Townsend, R., Milbrandt, J., Kiess, W., & Imai, S. (2007). Nampt/PBEF/Visfatin Regulates Insulin Secretion in ? Cells as a Systemic NAD Biosynthetic Enzyme Cell Metabolism, 6 (5), 363-375 DOI: 10.1016/j.cmet.2007.09.003

Yamada, T., Katagiri, H., Ishigaki, Y., Ogihara, T., Imai, J., Uno, K., Hasegawa, Y., Gao, J., Ishihara, H., Niijima, A., Mano, H., Aburatani, H., Asano, T., & Oka, Y. (2006). Signals from intra-abdominal fat modulate insulin and leptin sensitivity through different mechanisms: Neuronal involvement in food-intake regulation Cell Metabolism, 3 (3), 223-229 DOI: 10.1016/j.cmet.2006.02.001

Yoon, M., Yoshida, M., Johnson, S., Takikawa, A., Usui, I., Tobe, K., Nakagawa, T., Yoshino, J., & Imai, S. (2015). SIRT1-Mediated eNAMPT Secretion from Adipose Tissue Regulates Hypothalamic NAD+ and Function in Mice Cell Metabolism, 21 (5), 706-717 DOI: 10.1016/j.cmet.2015.04.002

Yoshino, J., & Imai, S. (2010). A Clock Ticks in Pancreatic ? Cells Cell Metabolism, 12 (2), 107-108 DOI: 10.1016/j.cmet.2010.07.006

Image via Poznyakov / Shutterstock.

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