Best and Worst of Neuroscience and Neurology – July 2015by Viatcheslav Wlassoff, PhD | August 10, 2015
Neuroscience is fascinating – every month we learn something new. And this new knowledge relates to some of the most fundamental processes in the brain that shape our daily life. The month of July wasn’t an exception. Quite a few exciting findings were published on various subjects in theoretical neurobiology and its biomedical applications.
On the 1st July, scientific community marked the birthday of Alfred Gilman. Dr Gilman received the 1994 Nobel Prize in Physiology and Medicine for his work on G-proteins. These transmembrane proteins, as every neuroscience student knows these days, are the most important components of cellular signaling. They are involved in practically all manner of intercellular communication between brain cells too.
Prion-like proteins and long-term memory maintenance
Despite recent progress in our understanding of brain functions, we still have only a limited knowledge about the formation and storage of long-term memories. A seminal paper published this month can be viewed as a serious breakthrough in this field.
Researchers have demonstrated that long-term memories are maintained by prion-like proteins. The protein called CPEB3 was shown to be involved in the process. Like typical prions involved in a variety of neurodegenerative disorders, CPEB3 can exist in soluble and aggregated forms. When we learn something, new synaptic connections are made and the soluble form of CPEB3 in the synapses gets converted into insoluble aggregates. These aggregates turn on the synthesis of proteins needed to maintain the memory.
New, better compounds for depression
Anti-depressants, such as Prozac and other selective serotonin re-uptake inhibitors (SSRIs), work slowly and produce appreciable effects only after many weeks or months of administration. They are also known to be associated with a number of side effects.
As a result, many medical professionals voice their concerns about the increasing use of SSRIs. However, new compounds called GABA-NAMS that work on a completely different mechanism may revolutionize the treatment of depression. In animal experiments, they were shown to treat depression in less than 24 hours with minimal side effects. This is a serious improvement compared to SSRIs, and the hopes are high that these drugs will soon be tested on humans.
Anti-malarials for treating Parkinson’s disease
Drug repurposing becomes an increasingly common strategy when it comes to looking for new approaches to treat various conditions. The reason for this lies in the fact that many pathological processes share common biochemical mechanisms. As a result, a drug developed for one condition may turn out to be helpful in treating something else.
The most resent, and rather remarkable, example of repurposing involves Parkinson’s disease. It turned out that drugs used for prevention and treatment of malaria, Chloroquine and Amodiaquine, reduce the symptoms and improve the behavior of rats with this disease. There is a hope that these drugs might be quickly developed into a treatment for humans.
Fingolimod, a drug for multiple sclerosis, as a treatment for Huntington’s disease
Another successful drug repurposing story came from the search for treatments for Huntington’s disease. It turned out that a 3-month course of fingolimod, a drug for multiple sclerosis, improved memory and restores synaptic plasticity in hippocampus in mice with Huntington’s disease. The drug has a good safety profile, and researchers currently plan a study on human patients.
Cross-talk between immune system and age-related cognitive decline
Last year, researchers from Stanford demonstrated that the blood of young rats reverses the cognitive decline in old animals. Continuing studies on this subject, the scientists found that the opposite is true when the blood of older animals circulates in the body of young rats.
It turned out that the blood of older animals contains increased amount of beta-2 microglobulin (B2M). B2M is a component of immune system but also participates in shaping the communication between brain cells. In the experiments, the increased amount of B2M in the blood was clearly linked with worsening performance in memory tests. Interestingly, the effect of B2M is reversible, and the cognitive abilities get restored once B2M level is decreased. The discovery might pave the way for developing targeted drugs for prevention of age-related cognitive decline.
Humans are probably not so good at distinguishing odors, after all
A paper on smell perception published in Science in 2014 claims that humans can distinguish at least a trillion odors. But a new paper published few weeks ago in eLife, a journal with significantly smaller Impact Factor, casts serious doubts on the validity of that claim.
This new paper shows that the number of smell heavily depends on the number of participants and the strictness of statistical tests used for the estimation. It also appears that the original claim is based on some unproven assumptions about the human smell perception, which is rather poorly understood at present. Nonetheless, the trillion odor claim is already making its way into the neuroscience textbooks. A case of bad science, perhaps?
Vitamin B12 provides no benefit in older people with moderate deficiency
The fact that the lack of vitamin B12 leads to serious problems in the nervous system is well established. Vitamin B12 supplementation provides obvious improvements in patients with severe deficiency. These days, vitamin B12 is also routinely prescribed to older patients with moderate and mild deficiency in the hope that the supplement will help to improve their cognitive and motor functions.
However, the results of new clinical trial show that B12 supplementation of such patients provides no benefits whatsoever. British researchers gave either B12 pills or placebo to a group of elderly (75 years old and above) patients for one year. At the end of the study, the scientists compared the patients performance in a battery of clinical tests. Surprisingly, not a single difference to the pre-trial results was spotted. Clearly, it’s a time to rethink the current strategy of B12 supplementation.
Tiny brain lesions, serious risk of stroke
Brain imaging provides lots of information about its state of health. Not all of this information, however, is taken into account by clinicians: the meaning or significance of certain changes in the brain is simply not always clear. One of such traditionally disregarded things is very small lesions which were always viewed as insignificant and normal even in healthy people. But the new findings published this month indicate that these lesions are associated with increased risk of stroke and even death. The risk can be as much as three times higher compared to the patients without lesions. This is clearly something to take into consideration for medical professional.
Antidepressants may affect cognitive development by interfering with REM sleep
The use of antidepressants has been growing fast in recent years. Many pediatricians even prescribe them to children with various disorders. The latter might be of serious concern, however, as these compounds tend to disturb the so-called “rapid eye movement” (REM) sleep. REM sleep is very important for converting our daytime experiences into memories. New findings suggest that REM sleep is particularly crucial during the periods of rapid brain remodeling, i.e. in children and adolescents, when lots of higher cognitive functions and skills get acquired and developed. Antidepressants seriously disturb REM sleep thus potentially affecting children’s ability to learn and adapt.
Sleep deprivation, not a good night’s sleep, might be beneficial after traumatic experience
Both conventional wisdom and medical advice say that a good night’s sleep helps to reduce the effects of traumatic events, such as intrusive memories and flashbacks. This might be wrong approach, however.
In a recent experiment, researchers subjected people who watched emotionally disturbing movies to either interrupted sleep at the sleep laboratory or allowed them to sleep at the comfort of their homes. It turned out that people from the sleep-deprived group were not as good at remembering the emotionally disturbing details of the movie. Sleep is known to consolidate memories. It appears that sleep deprivation might be helpful in preventing the consolidation of traumatic memories.
Dangour, A., Allen, E., Clarke, R., Elbourne, D., Fletcher, A., Letley, L., Richards, M., Whyte, K., Uauy, R., & Mills, K. (2015). Effects of vitamin B-12 supplementation on neurologic and cognitive function in older people: a randomized controlled trial American Journal of Clinical Nutrition DOI: 10.3945/ajcn.115.110775
Dumoulin Bridi, M., Aton, S., Seibt, J., Renouard, L., Coleman, T., & Frank, M. (2015). Rapid eye movement sleep promotes cortical plasticity in the developing brain Science Advances, 1 (6) DOI: 10.1126/sciadv.1500105
Fioriti, L., Myers, C., Huang, Y., Li, X., Stephan, J., Trifilieff, P., Colnaghi, L., Kosmidis, S., Drisaldi, B., Pavlopoulos, E., & Kandel, E. (2015). The Persistence of Hippocampal-Based Memory Requires Protein Synthesis Mediated by the Prion-like Protein CPEB3 Neuron, 86 (6), 1433-1448 DOI: 10.1016/j.neuron.2015.05.021
Fischell, J., Van Dyke, A., Kvarta, M., LeGates, T., & Thompson, S. (2015). Rapid Antidepressant Action and Restoration of Excitatory Synaptic Strength After Chronic Stress by Negative Modulators of Alpha5-Containing GABAA Receptors Neuropsychopharmacology DOI: 10.1038/npp.2015.112
Gerkin, R., & Castro, J. (2015). The number of olfactory stimuli that humans can discriminate is still unknown eLife, 4 DOI: 10.7554/eLife.08127
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
Porcheret, K., Holmes, E., Goodwin, G., Foster, R., & Wulff, K. (2015). Psychological Effect of an Analogue Traumatic Event Reduced by Sleep Deprivation SLEEP DOI: 10.5665/sleep.4802
Smith, L., He, Y., Park, J., Bieri, G., Snethlage, C., Lin, K., Gontier, G., Wabl, R., Plambeck, K., Udeochu, J., Wheatley, E., Bouchard, J., Eggel, A., Narasimha, R., Grant, J., Luo, J., Wyss-Coray, T., & Villeda, S. (2015). ?2-microglobulin is a systemic pro-aging factor that impairs cognitive function and neurogenesis Nature Medicine, 21 (8), 932-937 DOI: 10.1038/nm.3898
Windham, B., Deere, B., Griswold, M., Wang, W., Bezerra, D., Shibata, D., Butler, K., Knopman, D., Gottesman, R., Heiss, G., & Mosley, T. (2015). Small Brain Lesions and Incident Stroke and Mortality Annals of Internal Medicine, 163 (1) DOI: 10.7326/M14-2057
Wood, H. (2015). Neurodegenerative disease: Could fingolimod provide cognitive benefits in patients with Huntington disease? Nature Reviews Neurology, 11 (8), 426-426 DOI: 10.1038/nrneurol.2015.117
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