Best and Worst of Neuroscience and Neurology – April 2015by Viatcheslav Wlassoff, PhD | May 9, 2015
In this article, I will present a selection of research articles published in April. As usual, many new interesting findings were made public this month, and the selection presented in this article reflects mostly my personal opinion of their importance.
27 April was the birthday of Edward Moser, director of the Kavli Institute for Systems Neuroscience and Centre for Neural Computation in Trondheim, Norway, and the receiver of the last year’s Nobel Prize in Physiology and Medicine. Prof. Mozer is heralded for discovering the brain’s positioning system, which helps us navigate in space and works, in a way, similar to GPS.
This month, a number of interesting articles shedding light on how our brain works and how the memories are formed were published.
Being slightly overweight helps the aging brain
People who are slightly overweight tend to have fewer health problems in the older age. In the midst of the current obesity crisis, this fact is rarely mentioned by the popular media.
It turns out that metabolic processes behind this phenomenon are directly linked with the brain. The process involves an enzyme called NAMPT, which is involved in the generation of energy and is produced mostly in the adipose tissue. NAMPT is released from the fat cells and is used elsewhere in the body, including the brain. Low amounts of fat result in low levels of NAMPT and, as a consequence, an insufficient energy supply to the brain. Hypothalamus is particularly affected by the low level of NAMPT. This is important, since the hypothalamus is a key regulator of many physiological functions such as body temperature, blood pressure, sleep cycle and others.
Same metabolic regulator is involved in physical and mental activities
Both physical activities such as running, and mental activities such as memorizing require lots of energy. It turned out that this is not the only similarity between the two. The energy flow in both cases is controlled by the same key metabolic regulator.
Researchers found that the protein ERR-gamma that activates various metabolic pathways turns on fat-burning in muscles and sugar-burning in brain. It is known that activation of ERR-gamma energizes muscles. Mice with missing ERR? were shown to be a very poor learners. Researchers hypothesize that increasing the levels of ERR-gamma may help to enhance learning skills and pave the way to improve the treatment of learning disorders.
Molecular mechanisms behind memory formation further deciphered
Molecular mechanisms underlying the formation of memories remain poorly studied. New paper published this month by neuroscientists from Vanderbilt University makes an important contribution to our understanding of these processes.
Formation of memories involves the formation of dendritic spines, tiny filaments making electrochemical connections between neurons. Researchers have identified a key signalling protein, Asef2, involved in the process of adhering between dendrites and axons. In response to yet unidentified signals, Asef2 triggers the production of actin. Actin is a key component of cytoskeleton that makes possible cell movement and stabilizes the newly formed connections. Formation of dendritic spines is affected in many neurological conditions such as autism and Alzheimer’s disease. It is possible that this process can be restored by targeting the specific proteins involved.
Sleep as a management tool for Alzheimer’s?
Like most of other neurodegenerative conditions, Alzheimer’s disease currently has no effective treatments. But can a simple lifestyle modification, such as getting enough sleep, help in the management of this condition? At least, this appears to be true for the fruit flies with Alzheimer’s-like syndromes.
Scientists have shown that extra sleep helps to restore their ability to form new memories. It remains to be seen if such simple intervention can be helpful for human patients. It was recently shown that a short daytime nap can improve memory as much as 5-fold in healthy humans.
Complex nature of nicotine withdrawal symptoms
Quitting smoking is not an easy task. Nicotine appears to be a very addictive substance, and withdrawal symptoms such as anxiety contribute substantially to the failure of many smokers to get rid of the habit. In a new article published this month, researchers revealed specific neuronal circuits behind the withdrawal symptoms.
Researchers found that signals from two brain regions, the ventral tegmental area (part of the brain associated with pleasure and rewards) and the medial habenula, come together to the interpeduncular nucleus and trigger a number of processes, including the elevation of corticotropin releasing factors (CRF) level. The latter is known to be involved in response to the stress. This increased stimulation of interpeduncular nucleus triggers the feeling of anxiety. The good news is that the drugs blocking CRF receptors already exist, and it might be possible to use them to reduce the stimulation of interpeduncular nucleus and, thus, anxiety.
As usual, this month we have seen a number of publications that have changed our views on some important issues. We may consider them as negative developments, but gaining any knowledge is always a positive thing.
Alcohol consumption in early adulthood: unexpected impact on brain development
It is well known that excessive consumption of alcohol by teenagers affects their memory and learning ability. A new study by researchers at Duke University has now demonstrated that alcohol can also damage the brain of young adults.
The brain continues to mature until the mid-20s, and this is a period when many young people start to drink frequently. Researchers measured the long-term potentiation (LTP) in the hippocampus of rats exposed to the excess of alcohol at the age that corresponds to human early 20s. LTP is involved in the strengthening of synapses and thus the formation of memory, and it was clearly affected in the experimental animals. In addition, the dendritic spines in the hippocampus of rats appeared immature. Scientists think that excess alcohol in early adulthood disrupts the brain’s maturation process.
The impact of air pollution on brain health is seriously underestimated
Long-term exposure to air pollution is known to be damaging for health. Recent data indicate that brain health can also be affected by this environmental factor, as air pollution is statistically linked to increased risk of stroke, anxiety and suicide.
New findings published this month suggest that the damage may be more severe than previously thought. It was found that exposure to the fine particles found in the polluted air increases the risk of covert brain infarcts by as much as 46%. Covert brain infarct is a form of silent stroke which is associated with dementia and worsened cognitive functions.
Intense aggression: unexpected complexity
Extremely aggressive behavior in males is known to be linked to the elevated level of neurotransmitter serotonin. This is the same compound which is central for our feeling of happiness. The level of serotonin, however, is regulated by several other neurotransmitters.
A new study by Japanese researchers focused on the dorsal raphe nucleus – a major hub for serotonin in the brain – located in its most primitive part. Using a novel in vivo technique, researchers found that the intense aggression-linked surge in serotonin in this location is caused by the increased release of neurotransmitter glutamate in the dorsal raphe nucleus. The findings may help in identifying a suitable pharmaceutical target for developing drugs against psychopathy in humans. They also point to the importance of more probing investigations when we want to target specific conditions without affecting other important mechanisms in the brain.
Assumptions on gender-specific brain development proven wrong
The brains of males and females are rather different – certain parts are different in size and have different numbers of neurons, which are also differently connected. It was long assumed that the brain acquires its gender-specific characteristics during a short period of prenatal development, and once this period is over, the window for further changes is closed. But new findings published this month demonstrate that these assumptions are incorrect.
Researchers found that inhibiting of DNA methyltransferases, the enzymes involved in the repressing of genes, in preoptic area of the rats brain, may “un-silence” some genes and lead to masculinization of female brains. Female rats who received the injections of DNA methyltransferase inhibitors went on to develop more masculine brain feature. Moreover, these rats demonstrated typically male characteristics in their reproductive behavior. It would be interesting to investigate if some related processes in the human postnatal development may be linked to homosexuality.
Death of lactate shuttle theory?
The brain consumes one-fifth of all energy generated in the body. It was always believed that this extreme energy consumption is facilitated by the brain support cells, astrocytes, that produce energy from sugar and pass it to neurons. However, a new article published in Nature Communication this month is likely to prove that this lactate shuttle theory is wrong.
Using a new technique called 2-photon microscopy, the scientists observed the lactate consumption by different cells in the brain directly in real time. They found that neurons and not astrocytes take up glucose directly. Moreover, stimulation of cells led to the increased glucose consumption by neuron while no changes in the glucose consumption by astrocytes were observed. The findings are important – it appears that some chapters in the basic neuroscience textbooks will now need to be rewritten.
Dissel, S., Angadi, V., Kirszenblat, L., Suzuki, Y., Donlea, J., Klose, M., Koch, Z., English, D., Winsky-Sommerer, R., van Swinderen, B., & Shaw, P. (2015). Sleep Restores Behavioral Plasticity to Drosophila Mutants Current Biology DOI: 10.1016/j.cub.2015.03.027
Evans, J., Robinson, C., Shi, M., & Webb, D. (2015). The Guanine Nucleotide Exchange Factor (GEF) Asef2 Promotes Dendritic Spine Formation via Rac Activation and Spinophilin-dependent Targeting Journal of Biological Chemistry, 290 (16), 10295-10308 DOI: 10.1074/jbc.M114.605543
Lundgaard, I., Li, B., Xie, L., Kang, H., Sanggaard, S., Haswell, J., Sun, W., Goldman, S., Blekot, S., Nielsen, M., Takano, T., Deane, R., & Nedergaard, M. (2015). Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism Nature Communications, 6 DOI: 10.1038/ncomms7807
Nugent, B., Wright, C., Shetty, A., Hodes, G., Lenz, K., Mahurkar, A., Russo, S., Devine, S., & McCarthy, M. (2015). Brain feminization requires active repression of masculinization via DNA methylation Nature Neuroscience, 18 (5), 690-697 DOI: 10.1038/nn.3988
Pei, L., Mu, Y., Leblanc, M., Alaynick, W., Barish, G., Pankratz, M., Tseng, T., Kaufman, S., Liddle, C., Yu, R., Downes, M., Pfaff, S., Auwerx, J., Gage, F., & Evans, R. (2015). Dependence of Hippocampal Function on ERR?-Regulated Mitochondrial Metabolism Cell Metabolism, 21 (4), 628-636 DOI: 10.1016/j.cmet.2015.03.004
Risher, M., Fleming, R., Risher, W., Miller, K., Klein, R., Wills, T., Acheson, S., Moore, S., Wilson, W., Eroglu, C., & Swartzwelder, H. (2015). Adolescent Intermittent Alcohol Exposure: Persistence of Structural and Functional Hippocampal Abnormalities into Adulthood Alcoholism: Clinical and Experimental Research DOI: 10.1111/acer.12725
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
Wilker, E., Preis, S., Beiser, A., Wolf, P., Au, R., Kloog, I., Li, W., Schwartz, J., Koutrakis, P., DeCarli, C., Seshadri, S., & Mittleman, M. (2015). Long-Term Exposure to Fine Particulate Matter, Residential Proximity to Major Roads and Measures of Brain Structure Stroke, 46 (5), 1161-1166 DOI: 10.1161/STROKEAHA.114.008348
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
Zhao-Shea, R., DeGroot, S., Liu, L., Vallaster, M., Pang, X., Su, Q., Gao, G., Rando, O., Martin, G., George, O., Gardner, P., & Tapper, A. (2015). Increased CRF signalling in a ventral tegmental area-interpeduncular nucleus-medial habenula circuit induces anxiety during nicotine withdrawal Nature Communications, 6 DOI: 10.1038/ncomms7770
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