October brought us some new examples of how our lifestyle negatively impacts our health, be it stress, diet, or our sleep patterns. But it also revealed some new therapeutic targets in a number of brain-related pathologies. Here are the best and worst news I came across in October.
THE BEST
Cholesterol-lowering medication may improve the outcome of aneurysm repair surgeries
Statins are a class of cholesterol-lowering drugs. They protect blood vessels from atherosclerosis and stress, and they have been shown to be able to slow the progression of aneurysms. Therefore, a study published in Vascular aimed at evaluating how the use of statins could affect the outcomes of patients undergoing aortic aneurysm repair surgery.
The results showed that statin administration before surgery significantly lowered the postoperative mortality, as well as the incidence of complications after aortic repair. The data therefore shows that statin administration may be an effective prophylactic measure for patients undergoing aortic aneurysm repair.
A new target for post-stroke neuronal repair
The ability to repair damaged neuronal tissue would be of obvious importance for post-stroke recovery. A molecule named growth and differentiation factor 10 (GDF10) is known to be induced in neurons surrounding infarcted areas in mice, non-human primates and in humans. This molecule is also known to be able to promote the growth of axons in vitro in mouse, rat and human neurons.
New research published in Nature Neuroscience showed that GDF10 can also induce axonal growth in vivo and enhance functional recovery after stroke, thereby placing it as a potential therapeutic target for stroke patients.
A new player on the onset of seizures
A new discovery published in Nature Communications shed some light on the onset mechanisms of seizure disorders.
The authors found that there is a molecule named metal-regulatory transcription factor 1 (MTF1) onto which free zinc ions dock before the occurrence of an epileptic seizure. It had already been known that the concentration of zinc increases in the hippocampus before a spontaneous epileptic seizure, but now it was shown that after the docking of zinc onto MTF1 this molecule acts as a kind of switch for seizures by increasing the production of a specific calcium channel in neurons. Understanding this mechanism opens the door to the development of new strategies to prevent epileptic seizures.
B lymphocytes in multiple sclerosis
B lymphocytes, a type of white blood cells, have been emerging as contributors to the pathophysiology of multiple sclerosis (MS). Clinical trials applying B cell depletion therapy (BCDT) in people with MS have shown favorable results by being able to limit inflammation. Nevertheless, the mechanisms of B cell action in MS are still poorly understood.
The October issue of Science Translational Medicine published a study that offers new information on the role of B cells in MS. They identified a subset of B cells that produce the cytokine granulocyte macrophage–colony stimulating factor (GM-CSF) that contributes to MS pathogenesis. These cells are more frequent in MS patients and increase pro-inflammatory responses. Also, these cells seem to counterbalance the production of protective B cells.
Therapy with BCDT acted by normalizing the ratio of these types of B cells by decreasing the number of pathogenic GM-CSF–producing B cells. This study therefore unravels a way by which B cells can contribute to immune responses in MS, therefore contributing to a more selective targeting of disease processes in MS.
Five new genetic causes of glioma were identified
A huge genome-wide association study published in Nature Communications has identified five new genetic variants associated with glioma susceptibility. The study included a meta-analysis of data from more than 4,100 patients as well as additional data from almost 1,500 other glioma patients. These genetic variants are nothing more than a single letter difference in the DNA sequence, but they can increase the risk of glioma in those who carry it.
One of the variants found in the study is particularly aggressive as it increases by 23% the risk of developing glioblastoma, the most aggressive kind of glioma. The silver lining of this finding (which makes this good news) is that the identification of these variants may help develop new treatments against the disease or even allow preventive actions to be taken by their carriers.
THE WORST
Human endogenous viral DNA sequences in ALS
Throughout human evolution, a large number of viral sequences have been introduced into our genome. They are called human endogenous retroviral genes and they are usually silent, being regarded as “junk DNA”. But under pathological conditions they may become noticeable.
A report published in Science Translational Medicine suggests that human endogenous retroviral genes may be linked to the development of amyotrophic lateral sclerosis (ALS). The study showed that human endogenous retrovirus-K is reactivated in neurons of a subpopulation of patients with ALS, with a protein from this virus being able to cause the degeneration of neurons. Transgenic animals expressing this protein also developed ALS-like symptoms. There is still no effective treatment to ALS, but this finding raises the question of whether a therapeutic approach directed against these viral DNA sequences may potentially hamper the development of the disease.
Sleep, interrupted
We keep hearing different theories about the ideal sleep duration or the ideal sleep pattern. We also keep hearing about how poor quality of sleep affects our health.
New research published in the journal Sleep adds some new data to this issue. According to the study, awakening several times throughout the night has a higher negative impact on mood than an uninterrupted shorter amount of sleep. This work compared the effect of three consecutive nights of either forced awakenings, delayed bedtimes or uninterrupted sleep. The forced awakening group had the highest reduction in positive mood, being associated with shorter periods of deep sleep. Sleep interruption affected feelings of sympathy and friendliness and also the energy levels of the participants.
The impact of diet on autoimmune diseases of the nervous system
New evidence linking diet to autoimmune diseases of the central nervous system has emerged. Autoimmune diseases like MS are thought to be caused by an imbalance between anti- and pro-inflammatory autoimmune mechanisms. As can be read in the journal Immunity, using an animal model of autoimmune encephalomyelitis, it was observed that dietary long-chain fatty acids were able to promote the development and propagation of reactive immune cells in the intestinal wall, leading to increased neuronal injury.
An opposite action was found for short-chain fatty acids, which promoted the development and propagation of regulatory anti-inflammatory cells and decreased axonal damage. However, no effects of dietary fatty acids were observed when the intestine was germ-free, indicating that the intestinal microbiota may be directly involved in the mechanisms of fatty acid action. These findings once again illustrate the impact of diet on health and disease, suggesting that dietary interventions may have a therapeutic potential for autoimmune diseases such as MS.
High-fat diet and anxiety
A new study at the British Journal of Pharmacology gives yet another example of how diet can affect the brain. In order to study the link between metabolic and psychiatric disorders, mice were fed a high-fat diet and subjected to a metabolic and behavioral analysis.
It was revealed that an increased body weight and high blood sugar resulting from a high-fat diet can cause anxiety and depressive symptoms, along with observable changes in the brain. It was also tested whether the administration of an antidepressant could reverse the metabolic and behavioral changes induced by the high-fat diet. It was found that the beneficial effects of the antidepressant were highly reduced in mice receiving a high-fat diet. However, when such diet was interrupted, the metabolic changes and anxious symptoms were reverted.
Stress increases the risk of stroke
That stress is no good for your health is pretty much common sense by now, but new studies showing just how detrimental stress is keep emerging. Attempts to establish a link between stress and the risk of stroke had been fairly inconsistent. But a meta-analysis published in Neurology, including more than 138,000 participants who were followed for 3 to 17 years, may have cleared that question.
The study showed that people with high stress jobs had a higher risk of stroke than those with low stress jobs. The increased risk of stroke was more prominent in women with high stress jobs. It is possible that interventions to reduce work stress may decrease the risk of stroke, but that is a question that still needs research.
References
Finan PH, Quartana PJ, & Smith MT (2015). The Effects of Sleep Continuity Disruption on Positive Mood and Sleep Architecture in Healthy Adults. Sleep PMID: 26085289
Galiñanes EL, Reynolds S, Dombrovskiy VY, & Vogel TR (2015). The impact of preoperative statin therapy on open and endovascular abdominal aortic aneurysm repair outcomes. Vascular, 23 (4), 344-9 PMID: 25315791
Haghikia A, Jörg S, Duscha A, Berg J, Manzel A, Waschbisch A, Hammer A, Lee DH, May C, Wilck N, Balogh A, Ostermann AI, Schebb NH, Akkad DA, Grohme DA, Kleinewietfeld M, Kempa S, Thöne J, Demir S, Müller DN, Gold R, & Linker RA (2015). Dietary Fatty Acids Directly Impact Central Nervous System Autoimmunity via the Small Intestine. Immunity, 43 (4), 817-29 PMID: 26488817
Huang Y, Xu S, Hua J, Zhu D, Liu C, Hu Y, Liu T, & Xu D (2015). Association between job strain and risk of incident stroke: A meta-analysis. Neurology PMID: 26468409
Kinnersley B, Labussière M, Holroyd A, Di Stefano AL, Broderick P, Vijayakrishnan J, Mokhtari K, Delattre JY, Gousias K, Schramm J, Schoemaker MJ, Fleming SJ, Herms S, Heilmann S, Schreiber S, Wichmann HE, Nöthen MM, Swerdlow A, Lathrop M, Simon M, Bondy M, Sanson M, & Houlston RS (2015). Genome-wide association study identifies multiple susceptibility loci for glioma. Nature communications, 6 PMID: 26424050
Li R, Rezk A, Miyazaki Y, Hilgenberg E, Touil H, Shen P, Moore CS, Michel L, Althekair F, Rajasekharan S, Gommerman JL, Prat A, Fillatreau S, Bar-Or A, & Canadian B cells in MS Team (2015). Proinflammatory GM-CSF-producing B cells in multiple sclerosis and B cell depletion therapy. Science translational medicine, 7 (310) PMID: 26491076
Li S, Nie EH, Yin Y, Benowitz LI, Tung S, Vinters HV, Bahjat FR, Stenzel-Poore MP, Kawaguchi R, Coppola G, & Carmichael ST (2015). GDF10 is a signal for axonal sprouting and functional recovery after stroke. Nature neuroscience PMID: 26502261
Li W, Lee MH, Henderson L, Tyagi R, Bachani M, Steiner J, Campanac E, Hoffman DA, von Geldern G, Johnson K, Maric D, Morris HD, Lentz M, Pak K, Mammen A, Ostrow L, Rothstein J, & Nath A (2015). Human endogenous retrovirus-K contributes to motor neuron disease. Science translational medicine, 7 (307) PMID: 26424568
van Loo KM, Schaub C, Pitsch J, Kulbida R, Opitz T, Ekstein D, Dalal A, Urbach H, Beck H, Yaari Y, Schoch S, & Becker AJ (2015). Zinc regulates a key transcriptional pathway for epileptogenesis via metal-regulatory transcription factor 1. Nature communications, 6 PMID: 26498180
Zemdegs J, Quesseveur G, Jarriault D, Pénicaud L, Fioramonti X, & Guiard BP (2015). High fat diet-induced metabolic disorders impairs serotonergic function and anxiety-like behaviours in mice. British journal of pharmacology PMID: 26472268
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