The latest from http://brainblogger.com!
In the field of neuroscience and neurology, the end of last year was unusually fruitful for interesting and unexpected findings. There were fascinating developments both in fundamental research and in therapeutic treatment of brain diseases. As usual, the selection of publications presented here reflects my opinion of their importance.
On 11 December, the scientific community marked the birthday of American neuroscientist Paul Greengard. Greengard’s research helped to establish the detailed biochemical mechanisms of neural transduction and laid the foundation for further investigations of brain function. He received the Nobel Prize for Physiology or Medicine in recognition of his achievements in the field.
New therapy for chronic pain syndrome
Millions of people around the world suffer from chronic pain. New treatment based on already existing drugs may address this problem. In a new article published this month, researchers suggested to use a combination of levodopa, a drug against Parkinson’s disease, and a non-steroidal anti-inflammatory drug. In the animal experiments, the scientists demonstrated that the combination target the affected neural circuits and completely eliminates pain.
Researchers are currently applying for clinical trials of this drug combination in humans suffering from chronic pain.
New approach to target Alzheimer’s disease
Alzheimer’s and other neurodegenerative diseases are characterized by gradual accumulation of protein deposits such as beta-amyloids that eventually damage the neurons. It turned out, however, that this accumulation is not a one-way process. Neurons also have a mechanism for “garbage disposal” that, in normal cells, prevents deposit formations. A new drug, Rolipram, can activate the “garbage disposal” system and thus accelerate the removal of unwanted toxic proteins. A paper published this month demonstrates that the drug is capable of slowing down the disease developments in the mouse models.
Diabetes drug slows down progression of Huntington’s disease
At present, we don’t have any effective therapeutic interventions to treat or even slow down Huntington’s disease. However, a new article published this month may change this situation. Californian researchers found that an existing drug previously tested for diabetes slows down the development of symptoms of Huntington’s disease. The compound, known as KD3010, was shown to reduce neurodegeneration and improve motor function and survival in the experiments on animals.
The compound was already shown to be safe in humans, which means that its testing and introduction to the clinical use can be done much faster than usual.
DNA methylation: a likely code for memory formation
Despite decades of research, the exact molecular mechanisms of long-term memory formation remain mostly hypothetical. But it appears that a potential breakthrough was made this month by scientists from Germany.
The researchers demonstrated that formation of memory is associated with DNA methylation in neurons. Methylation modifies the backbone of DNA by chemically labeling specific sites. It is likely that methylation provides some sort of code for formation of memory. Deciphering this code will help us understand how memories are formed and stored in our brain.
Discovery shows how herpes simplex virus reactivates in neurons to trigger disease
Herpes simplex virus (HSV), a virus that causes cold sores and more serious diseases such as encephalitis, affects around 90% of humans. Normally, the virus lies dormant in some neurons of the brain. It is well known, however, that stress triggers the reactivation of virus. The mechanism behind this effect was unknown.
Recently, researchers from the University of North Carolina found that reactivation involves JNK pathway in neurons and the consequent escape of virus from neurons. The findings might help in developing an effective therapy against diseases caused by this virus.
Sadness may lead to other diseases through inflammation pathways
There are plenty of evidences that feeling sad for extended periods of time may lead to other diseases, but the mechanism behind this phenomenon was unknown. New research data shows that stress and feeling of sadness increase the level of stress-linked opioids in the brain, which triggers the rise of inflammatory protein levels in the blood. This, in turn, alters the response of immune system and makes the body more vulnerable to other illnesses such as cardiovascular problems and stroke. The effect is particularly strong in people suffering from major depression.
More research will be needed to establish how co-morbidities caused by prolonged stress can be prevented.
Too much TV watching at young age affects future cognitive functions
The fact that couch potatoes tend to have worse cognitive functions is well established. Even more interesting, recent findings show that watching too much TV as a young adult affects cognitive functions even 25 years later.
The results of a longitudinal study published this month show that people who watched TV for more than three hours a day when they were younger demonstrated poorer performance in a number of cognitive tests. The results were even worse when excessive TV watching was combined with the low level of physical activity. It appears that parents who restrict their kids from watching TV are right, after all.
IQ-improving interventions are not effective
We are born with different mental abilities, and the differences are often visible already in the early childhood. Psychologists always argued that early interventions aimed at improving the cognitive abilities can help children to develop higher IQ level. The results of the latest meta-analysis of published data covering 7,584 young children, however, come as a serious setback.
The effect of interventions appears to fade out once the intervention program is finished. The findings cast doubts on the efficiency of early intervention programs such as Head Start in the USA.
Treating prostate cancer by testosterone-lowering therapy increases risk of Alzheimer’s disease
Androgen-deprivation therapy (ADT) is one of the most efficient methods of treating prostate cancer. However, testosterone is important for protecting brain from neurodegenerative diseases. A study published this month demonstrated that men undergoing ADT are almost twice more likely to develop Alzheimer’s disease. Researchers believe that increased risk of Alzheimer’s is an adverse effect of therapy, but further studies are needed before any changes to clinical practice are introduced.
Reduced grey matter volume and behavioral problems in young people
Reduction in the grey matter volume within the amygdala, insula, and prefrontal cortex is associated with antisocial and aggressive behavior in younger people. This is the conclusion of researchers who systematically compared the brain differences in developing youths. The authors went through the brain imaging data from 13 published studies including 394 young adults with behavioral problems and 350 normally behaving youths.
Although the data demonstrate the connection between behavior and brain structure, it is not yet clear to what extent these structural differences are caused by other factors such as maltreatment in childhood and substance abuse during pregnancy.
Cliffe, A., Arbuckle, J., Vogel, J., Geden, M., Rothbart, S., Cusack, C., Strahl, B., Kristie, T., & Deshmukh, M. (2015). Neuronal Stress Pathway Mediating a Histone Methyl/Phospho Switch Is Required for Herpes Simplex Virus Reactivation Cell Host & Microbe, 18 (6), 649-658 DOI: 10.1016/j.chom.2015.11.007
Dickey, A., Pineda, V., Tsunemi, T., Liu, P., Miranda, H., Gilmore-Hall, S., Lomas, N., Sampat, K., Buttgereit, A., Torres, M., Flores, A., Arreola, M., Arbez, N., Akimov, S., Gaasterland, T., Lazarowski, E., Ross, C., Yeo, G., Sopher, B., Magnuson, G., Pinkerton, A., Masliah, E., & La Spada, A. (2015). PPAR-? is repressed in Huntington’s disease, is required for normal neuronal function and can be targeted therapeutically Nature Medicine, 22 (1), 37-45 DOI: 10.1038/nm.4003
Halder, R., Hennion, M., Vidal, R., Shomroni, O., Rahman, R., Rajput, A., Centeno, T., van Bebber, F., Capece, V., Vizcaino, J., Schuetz, A., Burkhardt, S., Benito, E., Sala, M., Javan, S., Haass, C., Schmid, B., Fischer, A., & Bonn, S. (2015). DNA methylation changes in plasticity genes accompany the formation and maintenance of memory Nature Neuroscience, 19 (1), 102-110 DOI: 10.1038/nn.4194
Hoang, T., Reis, J., Zhu, N., Jacobs, D., Launer, L., Whitmer, R., Sidney, S., & Yaffe, K. (2016). Effect of Early Adult Patterns of Physical Activity and Television Viewing on Midlife Cognitive Function JAMA Psychiatry, 73 (1) DOI: 10.1001/jamapsychiatry.2015.2468
Myeku, N., Clelland, C., Emrani, S., Kukushkin, N., Yu, W., Goldberg, A., & Duff, K. (2015). Tau-driven 26S proteasome impairment and cognitive dysfunction can be prevented early in disease by activating cAMP-PKA signaling Nature Medicine, 22 (1), 46-53 DOI: 10.1038/nm.4011
Nead, K., Gaskin, G., Chester, C., Swisher-McClure, S., Dudley, J., Leeper, N., & Shah, N. (2015). Androgen Deprivation Therapy and Future Alzheimers Disease Risk Journal of Clinical Oncology DOI: 10.1200/JCO.2015.63.6266
Prossin, A., Koch, A., Campbell, P., Barichello, T., Zalcman, S., & Zubieta, J. (2015). Acute experimental changes in mood state regulate immune function in relation to central opioid neurotransmission: a model of human CNS-peripheral inflammatory interaction Molecular Psychiatry, 21 (2), 243-251 DOI: 10.1038/mp.2015.110
Protzko, J. (2015). The environment in raising early intelligence: A meta-analysis of the fadeout effect Intelligence, 53, 202-210 DOI: 10.1016/j.intell.2015.10.006
Ren, W., Centeno, M., Berger, S., Wu, Y., Na, X., Liu, X., Kondapalli, J., Apkarian, A., Martina, M., & Surmeier, D. (2015). The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain Nature Neuroscience, 19 (2), 220-222 DOI: 10.1038/nn.4199
Rogers, J., & De Brito, S. (2016). Cortical and Subcortical Gray Matter Volume in Youths With Conduct Problems JAMA Psychiatry, 73 (1) DOI: 10.1001/jamapsychiatry.2015.2423
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