The last month, in my opinion, was particularly fruitful for new, interesting publications. In fact, I was struggling when deciding which of them to select for this review. Quite a few articles addressed fundamental questions about basic mechanisms of brain functioning, neurodegenerative diseases and evolution. Several important discoveries were made on new applications and treatments with existing drugs. Some medicines were shown to have unexpected side effects.
Although I couldn’t cover everything important in this review, I’ll address the most interesting topics in the follow-up weekly articles.
In May, the scientific community marked the birthday of Sidney Altman, 1989 Nobel Laureate in Chemistry. Dr Altman has discovered catalytic properties of RNA. The discovery not only changed how we view this essential molecule of life in evolutionary terms, but also attracted enormous and ever-growing interest to the multiple functions of RNA in human body, both in normal and diseased states. More recent studies have revealed the critical role of RNA in the vital processes in human brain.
Amyloid-beta is part of normal innate immune system
Amyloid-beta is well-known for its negative contribution to the development of Alzheimer’s disease. Much less is known about its normal functions though. It turns out that this protein is a normal part of the body’s innate immune system responsible for defence against infections.
In experiments on model animals, researchers have shown that oligomers of amyloid-beta clump together on the surface of pathogens such as Candida or Salmonella and prevent them from attacking healthy host cells. Mice expressing human amyloid-beta survived much longer after the introduction of Salmonella infection into their brains.
Faster metabolism enabled larger brain development in humans
A closer look into the metabolism of our closest evolutionary relatives, other hominids, revealed that humans have much higher metabolism rate.
Calculations show that after adjusting to body weight, humans consume 400 more calories than chimps, 635 more calories than gorillas and 820 more calories than orangutans. We also have much larger fat deposits in our body. It is well know that the human brain consumes up to 20% of total body energy. Researchers believe that faster metabolism enabled us to develop a larger brain, while fat reserves were used to fuel this faster metabolic rates.
Heart medicine may help in treating Alzheimer’s disease
It appears that commonly available heart medicine, clopidogrel, might be useful in treating Alzheimer’s disease.
Swedish scientists uncovered a new mechanism behind the build-up of plaques in the brain’s blood vessels. Amyloid-beta, one of the major proteins involved in the development of Alzheimer’s disease, sticks to the surface of blood platelets, causing their aggregation and rapid formation of plaques. These plaques disrupt the supply of oxygen and nutrients to the brain cell and cause them to die. Clopidogel, a platelet activation inhibitor, slows down this process and helps to reduce the number of plagues in the deep brain tissue. The experiments were done on animal models, and at present it is not yet clear if the results are transferable to humans.
Mechanism of chemotherapy damage to the brain explained
Many cancer patients undergoing chemotherapy develop a condition often referred to as “chemo brain”. Chemotherapy can change cognitive abilities and cause problems with memory and difficulties concentrating.
New findings published this month demonstrate that the reason behind these symptoms is the impaired release of neurotransmitters such as dopamine and serotonin. Better understanding of this mechanism may help in developing therapeutic strategies for preventing or minimizing the negative consequences of chemotherapy to the brain functions.
Aspirin substantially reduces risk of major stroke after transient ischaemic attack
The humble aspirin, which doctors around the world use for a wide range of conditions, has found yet another important application. It turns out that taking aspirin immediately after transient ischaemic attack (TIA) reduces the chances of consequent major stroke by 70-80%. TIA, or a mini-stroke, often preceeds major stroke. Mini-stroke is a serious warning sign that calls for specialist assessment.
The new findings demonstrate that taking 300 mg of aspirin immediately after TIA, even without assessment, can help to avoid potential major troubles.
Prolonged use of gut-affecting antibiotics stops the growth of new brain cells
Many antibiotics affect gut flora and, if used for along period of time, may kill many beneficial species of bacteria in the intestines.
Article published this month demonstrates that such prolonged antibiotic treatments also affect the brain, at least in animal models. Specifically, they affect neurogenesis in hippocampus and consequently lead to worsening memory. Fortunately, the use of probiotics can reverse this effect.
Mitoxantrone increases risk of colorectal cancer in MS patients
The use of many modern drugs is associated with long-term side effects that are difficult, if not impossible, to predict. An article published this month demonstrated that mitoxantrone, a drug for treatment of aggressive types of multiple sclerosis (MS), increases the risk of colorectal cancer.
The study shows that rate of colorectal cancer is three times higher in MS patients who used this drug compared to general population. Despite the risk, researchers believe that mitoxantrone still should be used when MS is progressing fast and no other treatments are available. They do, however, recommend that MS patients on this drug should regularly undergo colonoscopy for early diagnostics of potential tumours.
Full recovery from concussion takes very long time in children and young adults
Concussions are common in many sports, and many recent studies aimed to investigate their long-term consequences. Young athletes usually return to sports few weeks after concussion, as this time period is believed to be sufficient for full recovery.
However, a new study published this month demonstrate that this assumption is not correct. In fact, full recovery may take up to two years. The children and young adults recruited for the study demonstrated poorer performance in cognitive motor integration test compared to healthy peers well after they were cleared to participate in sports. The authors believe that the fragility of young, developing brain is the factor behind the observed phenomenon.
Repeated radiotherapy for brain tumours is damaging for healthy brain cells
Brain tumours are commonly treated by repeated doses of radiation therapy. The rationale for such approach is based on the assumption that using the reduced repeated doses prevents serious damage to the supporting cells of the brain, oligodendrocyte progenitor cells (OPC). Fully developed neurons don’t have capacity for self-renewal and therefore are believed to be not particularly sensitive to radiation. OPCs, on the other hand, get damaged and killed alongside cancer cells. It was believed that reduced repeated doses may help minimizing the damage to these cells.
New findings suggest that this assumption is wrong. Damage caused by first radiation dose kills some OPCs and stimulate the remaining cells to reproduce faster. Reproducing cells are particularly vulnerable to radiation, and consequent doses kill OPCs in large numbers. This eventually causes damage to the neurons as well. Researchers believe that the use of a single large radiation dose instead of repeated smaller doses might be more effective and safer for healthy brain cells.
Anti-seizure drug may cause birth defects
A drug commonly used to treat epilepsy, neuropathic pain, anxiety disorder and a number of other conditions was found to be associated with major birth defects when used by pregnant women.
The drug pregabalin, when taken during the first trimester of pregnancy, led to three times higher rate of birth defects, including heart defects and structural problems in CNS, compared to women who did not take this anti-seizure medication. The author call for caution when using this drug during pregnancy and for additional foetal monitoring.
Begolly, S., Shrager, P., Olschowka, J., Williams, J., & O’Banion, M. (2016). Fractionation spares mice from radiation-induced reductions in weight gain but does not prevent late oligodendrocyte lineage side effects International Journal of Radiation Oncology*Biology*Physics DOI: 10.1016/j.ijrobp.2016.05.005
Buttmann, M., Seuffert, L., Mäder, U., & Toyka, K. (2016). Malignancies after mitoxantrone for multiple sclerosis Neurology, 86 (23), 2203-2207 DOI: 10.1212/WNL.0000000000002745
Dalecki, M., Albines, D., Macpherson, A., & Sergio, L. (2016). Prolonged cognitive–motor impairments in children and adolescents with a history of concussion Concussion DOI: 10.2217/cnc-2016-0001
Donner, L., Falker, K., Gremer, L., Klinker, S., Pagani, G., Ljungberg, L., Lothmann, K., Rizzi, F., Schaller, M., Gohlke, H., Willbold, D., Grenegard, M., & Elvers, M. (2016). Platelets contribute to amyloid- aggregation in cerebral vessels through integrin IIb 3-induced outside-in signaling and clusterin release Science Signaling, 9 (429) DOI: 10.1126/scisignal.aaf6240
Hankey, G. (2016). The benefits of aspirin in early secondary stroke prevention The Lancet DOI: 10.1016/S0140-6736(16)30511-6
Kaplan, S., Limbocker, R., Gehringer, R., Divis, J., Osterhaus, G., Newby, M., Sofis, M., Jarmolowicz, D., Newman, B., Mathews, T., & Johnson, M. (2016). Impaired Brain Dopamine and Serotonin Release and Uptake in Wistar Rats Following Treatment with Carboplatin ACS Chemical Neuroscience, 7 (6), 689-699 DOI: 10.1021/acschemneuro.5b00029
Kumar, D., Choi, S., Washicosky, K., Eimer, W., Tucker, S., Ghofrani, J., Lefkowitz, A., McColl, G., Goldstein, L., Tanzi, R., & Moir, R. (2016). Amyloid- peptide protects against microbial infection in mouse and worm models of Alzheimers disease Science Translational Medicine, 8 (340), 340-340 DOI: 10.1126/scitranslmed.aaf1059
Möhle, L., Mattei, D., Heimesaat, M., Bereswill, S., Fischer, A., Alutis, M., French, T., Hambardzumyan, D., Matzinger, P., Dunay, I., & Wolf, S. (2016). Ly6Chi Monocytes Provide a Link between Antibiotic-Induced Changes in Gut Microbiota and Adult Hippocampal Neurogenesis Cell Reports, 15 (9), 1945-1956 DOI: 10.1016/j.celrep.2016.04.074
Pontzer, H., Brown, M., Raichlen, D., Dunsworth, H., Hare, B., Walker, K., Luke, A., Dugas, L., Durazo-Arvizu, R., Schoeller, D., Plange-Rhule, J., Bovet, P., Forrester, T., Lambert, E., Thompson, M., Shumaker, R., & Ross, S. (2016). Metabolic acceleration and the evolution of human brain size and life history Nature, 533 (7603), 390-392 DOI: 10.1038/nature17654
Winterfeld, U., Merlob, P., Baud, D., Rousson, V., Panchaud, A., Rothuizen, L., Bernard, N., Vial, T., Yates, L., Pistelli, A., Ellfolk, M., Eleftheriou, G., de Vries, L., Jonville-Bera, A., Kadioglu, M., Biollaz, J., & Buclin, T. (2016). Pregnancy outcome following maternal exposure to pregabalin may call for concern Neurology, 86 (24), 2251-2257 DOI: 10.1212/WNL.0000000000002767
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