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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.
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.
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.
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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