Best and Worst of Neuroscience and Neurology – July 2016




Hundreds of articles published this month further advanced our knowledge of neuroscience. Lots of new discoveries published in July relate to some of the most fundamental processes in the brain that shape our daily life, as well as to the practical problems doctors have to deal with on a regular basis. The selection of articles presented here reflects my personal opinion about their importance – there were many more interesting articles that simply could not be covered by this short review.

In the beginning of July, scientific community marked the birthday of Alfred Gilman, who received the 1994 Nobel Prize in Physiology and Medicine for his work on G-proteins. These days, the description of G-proteins and their functions can be found in every textbook on physiology and neurology, as they are heavily involved in the processes of intercellular communication. Even in this review G-proteins are mentioned in relation to some recent findings.

 

THE BEST

Breast-fed pre-term infants develop higher IQ later in life

New observational study on pre-term infants confirm the importance of feeding them with breast milk. The infants who received predominantly breast milk during the first 28 days of life had higher IQ and better cognitive and motor functions at age 7. MRI study demonstrated that at this age the breast-fed children had larger volume of deep nuclear grey matter, which plays important role in signal processing and connecting different parts of brain.

Mechanism of Levodopa-induced dyskinesia uncovered

Levodopa is essential for treating patients with Parkinson’s disease, but unfortunately many patients develop undesirable side effects such as dyskinesia, involuntary rapid repetitive movements, after several years on the drug. Researchers have uncovered that the development of dyskinesia is linked to the changes in methylation of certain genes, as levodopa can change the expression of DNA methylases. Methylation affects gene expression and results in altered amount of corresponding proteins, thus disturbing the normal homeostasis. Experiments on animals show that drug therapies aimed at amending the DNA methylation level can reduced dyskinesia symptoms. 

Slow action of antidepressants explained

Most commonly used antidepressant from the serotonin reuptake inhibitors family are know to take up to 2 months to start producing positive effects in the patients. Researchers have now discovered the molecular mechanism responsible for this slow action. It turned out that in people with depression, the signalling G-protein molecules involved in the response to the drug are bound to the lipid rafts on the membranes of neurons where they cannot effectively participate in the signalling response. The study point to a potential approach that may improve the efficacy of antidepressants.

Anti-cancer drug promising for treating Alzheimer’s disease

An FDA-approved anti-cancer drug pazopanib, an inhibitor of tyrosine kinase, was shown to reduce the level of phosphorylation of tau-protein, one of the key culprits in the development of Alzheimer’s disease. In laboratory animals, the effect of the drug led to the improved clearance of toxic proteins from the brain. The drug is known to penetrate the blood-brain barrier and is effective in the doses half of those used in cancer treatment. In addition, pazopanib causes few side effects. The use of pazopanib in human subjects with Alzheimer’s requires further investigations. 

fMRI helped to visualize brain activity during hypnosis

Hypnosis gradually emerged as a promising form of psychotherapy, but our knowledge of brain processes in hypnotized state is still remains in its infancy. Researchers used fMRI to study the brain of people during hypnosis sessions. They found that in hypnotized people the activity of dorsal anterior cingulate is decreased, the connectivity between dorsolateral prefrontal cortex and the insula is increased, and the connectivity between dorsolateral prefrontal complex and the default mode network is reduced. These changes reflect the reduced state of worrying, increased brain control over processes in the body, and reduced awareness of one’s actions. Interestingly, these changes were most prominent only among highly hypnotizable people, which represent around 10% of general population.

 

THE WORST

Antibiotics increase frequency of manic episodes in psychiatric patients

It is well established that the composition of bacterial microbiome in the gut influence the work of our brain – this phenomenon is referred to as the gut brain axis. It appears that the connection is rather prominent in people with psychiatric disorders. Recent study suggests that people with serious mental illnesses such as bipolar syndrome, schizophrenia or major depression, are more likely to experience manic episode at the time when they are treated with antibiotics. Antibiotics are known to disrupt the bacterial flora in the gastrointestinal tract. This disruption may, in turn, lead to behavioural alterations. Researchers suggest that preventive treatments minimizing the use of antibiotics in psychiatric patients may reduce the frequency of manic episodes. 

No link between traumatic brain injury and Alzheimer’s disease

Large number of previous studies reported association between traumatic brain injury (TBI) and the development of neurodegenerative diseases such as Alzheimer’s later in life. The study published this month questions this conclusion. By analysing data from over 7,000 older adults (the largest cohort for this kind of study reported so far), researchers found a strong positive association between TBI and Parkinson’s disease, but no association between TBI and either Alzheimer’s disease or  dementia. Further work is needed to establish the mechanisms of and the factors influencing post-TBI neurodegeneration. 

Potential dangers of transcranial direct current stimulation (tDCS)

Transcranial direct current stimulation (tDCS) is becoming a popular approach to enhance brain functions. tDSC devices are simple, and the practice of self-administering them grew in popularity in recent years. This trend alarms researchers who warned in the open letter that such DIY approach may lead to unintended consequences. The letter published by scientists this month points to the fact that the method is still very new and it is not even known how the stimulation causes positive effects. It is also not clear how tDCS affects the surrounding areas of the brain that are not directly targeted, and what are the effects of larger accumulated doses administered over longer periods of time. The effectiveness of the method also varies from person to person, and there is a possibility that small changes in the electrode placement and frequency may lead to undesirable effects. 

Link betwen Alzheimer’s and brain blood vessels problems underestimated

Although risk factors associated with dementia and Alzheimer’s disease are well studied, the role of brain blood vessels received very little attention. Recent study demonstrated that the importance of this factor was clearly underestimated. Atherosclerosis (plaques in the larger brain arteries) and arteriolosclerosis (hardening of the smaller artery walls) strongly correlate with the chances of having dementia. Problems with blood vessels in the brain also correlated significantly with reduced cognitive abilities and performance in memory tests. 

Reduced physical activity after menopause linked to changes in brain

Post-menopausal women often experience weight gain. This was often explained by the changes in hormonal status. New evidences, however, suggest that this phenomenon is associated with brain changes, more specifically with the reduction in dopamine signalling level. This leads to decreased stimulation of pleasure centre and lack of motivation for being more physically active. Activation of dopamine receptors may potentially reverse this process.

 

Bibliography:

Mandy B. Belfort, MD, MPH et al. Breast Milk Feeding, Brain Development, and Neurocognitive Outcomes: A 7-Year Longitudinal Study in Infants Born at Less Than 30 Weeks’ Gestation. The Journal of Pediatrics, July 2016 DOI: 10.1016/j.jpeds.2016.06.045

A. Figge, K. L. Eskow Jaunarajs, D. G. Standaert. Dynamic DNA Methylation Regulates Levodopa-Induced Dyskinesia. Journal of Neuroscience, 2016; 36 (24): 6514 DOI: 10.1523/JNEUROSCI.0683-16.2016

Samuel J. Erb, Jeffrey M. Schappi, Mark M. Rasenick. Antidepressants Accumulate in Lipid Rafts Independent of Monoamine Transporters to Modulate Redistribution of the G protein, G?s. Journal of Biological Chemistry, 2016; jbc.M116.727263 DOI: 10.1074/jbc.M116.727263

Monica Javidnia, Michaeline Hebron, Hannah J Brown, Charbel E-H Moussa. Pazopanib Is a Potential Therapeutic for Tauopathies. AAIC 2017, July 16-20, London. Abstract ID: a8677.

Heidi Jiang, Matthew P. White, Michael D. Greicius, Lynn C. Waelde, and David Spiegel. Brain Activity and Functional Connectivity Associated with Hypnosis. Cerebral Cortex, July 2016 DOI: 10.1093/cercor/bhw220

Robert Yolken, Maria Adamos, Emily Katsafanas, Sunil Khushalani, Andrea Origoni, Christina Savage, Lucy Schweinfurth, Cassie Stallings, Kevin Sweeney, Faith Dickerson. Individuals hospitalized with acute mania have increased exposure to antimicrobial medications. Bipolar Disorders, 2016; DOI: 10.1111/bdi.12416

Paul K. Crane, Laura E. Gibbons, Kristen Dams-O’Connor, Emily Trittschuh, James B. Leverenz, C. Dirk Keene, Joshua Sonnen, Thomas J. Montine, David A. Bennett, Sue Leurgans, Julie A. Schneider, Eric B. Larson. Association of Traumatic Brain Injury With Late-Life Neurodegenerative Conditions and Neuropathologic Findings. JAMA Neurology, 2016; DOI: 10.1001/jamaneurol.2016.1948

Rachel Wurzman, Roy H. Hamilton, Alvaro Pascual-Leone, Michael D. Fox. An open letter concerning do-it-yourself users of transcranial direct current stimulation. Annals of Neurology, 2016; 80 (1): 1 DOI: 10.1002/ana.24689

Zoe Arvanitakis, Ana W Capuano, Sue E Leurgans, David A Bennett, Julie A Schneider. Relation of cerebral vessel disease to Alzheimer’s disease dementia and cognitive function in elderly people: a cross-sectional study. The Lancet Neurology, 2016; DOI: 10.1016/S1474-4422(16)30029-1

Young-Min Park, Jill A. Kanaley, Jaume Padilla, Terese Zidon, Rebecca J. Welly, Matthew J. Will, Steven L. Britton, Lauren G. Koch, Gregory N. Ruegsegger, Frank W. Booth, John P. Thyfault, Victoria J. Vieira-Potter. Effects of intrinsic aerobic capacity and ovariectomy on voluntary wheel running and nucleus accumbens dopamine receptor gene expression. Physiology & Behavior, 2016; 164: 383 DOI: 10.1016/j.physbeh.2016.06.006

 

 

Viatcheslav Wlassoff, PhD

Viatcheslav Wlassoff, PhD, is a scientific and medical consultant with experience in pharmaceutical and genetic research. He has an extensive publication history on various topics related to medical sciences. He worked at several leading academic institutions around the globe (Cambridge University (UK), University of New South Wales (Australia), National Institute of Genetics (Japan). Dr. Wlassoff runs consulting service specialized on preparation of scientific publications, medical and scientific writing and editing.
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