Neuroscience
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Multiple sclerosis (MS) is a progressive condition affecting the central nervous system (CNS), and is characterized by the development of demyelinated lesions and plaques in the brain and spinal cord. Exercise is beneficial against dementia in elderly patients, so we investigated the effects of exercise on memory in relation to hippocampal demyelination and neuroplasticity in a mouse model of MS (experimental autoimmune encephalomyelitis [EAE]). Mice were randomly divided into three groups: Sham, EAE, and EAE and exercise (EAE+EX). ⋯ We found decreased memory ability in EAE mice, accompanied by impaired myelination, increased apoptosis and cell proliferation, and decreased BDNF in the hippocampus. The memory decline and changes in demyelination, apoptosis, BDNF, and cell proliferation were partially reversed in EAE+EX mice. Our findings suggest that in patients with MS, regular exercise may benefit cognitive function by rescuing some hippocampal cellular and molecular impairments.
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Inward rectifying potassium - Kir - channels drive the resting potential to potassium reversal potential and, when disrupted, might be related to muscular diseases. Recently, Thyrotoxic Periodic Paralysis (TPP) has emerged as a channelopathy related to mutations in KCNJ18 gene, which encodes Kir2.6 channel. TPP is a neuromuscular disorder characterized by a triad of muscle weakness, hypokalemia, and thyrotoxicosis, the latter being essential for the crisis. ⋯ The mutant D252N Kir2.6 channel also showed a substantial reduction of ∼51% in membrane abundance relative to WT channel. Our study describes the functional consequences of a single amino acid change in Kir2.6 channel. Further analysis regarding hormonal conditions and Kir channel expression are required to provide new clues about the TPP pathophysiology.
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Stress-induced neural injuries are closely linked to the pathogenesis of various neuropsychiatric disorders and psychosomatic diseases. We and others have previously demonstrated certain protective effects of epigallocatechin-3-gallate (EGCG) in stress-induced cerebral impairments, but the underlying protective mechanisms still remain poorly elucidated. Here we provide evidence to support the possible involvement of PKCα and extracellular signal-regulated kinase 1/2 (ERK1/2) signaling pathways in EGCG-mediated protection against restraint stress-induced neural injuries in rats. ⋯ Furthermore, the stress-induced decrease of PKCα and ERK1/2 expression and phosphorylation was significantly attenuated by EGCG and to a less extent by GTP administration. Additionally, EGCG supplementation restored the production of adenosine triphosphate (ATP) and the expression of a key regulator of cellular energy metabolism, the peroxisome proliferators-activated receptor-γ coactivator-1α (PGC-1α), in stressed animals. In conclusion, PKCα and ERK1/2 signaling pathways as well as PGC-1α-mediated ATP production might be involved in EGCG-mediated protection against stress-induced neural injuries.
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Irreversible vision loss due to disease or age is responsible for a reduced quality of life. The experiments in this study test the hypothesis that the α7 nicotinic acetylcholine receptor agonist, PNU-282987, leads to the generation of retinal neurons in an adult mammalian retina in the absence of retinal injury or exogenous growth factors. ⋯ If retinas were treated with the alpha7 nAChR antagonist, methyllycaconitine, before agonist treatment, BrdU-positive cells were significantly reduced. As adult mammalian neurons do not typically regenerate or proliferate, these results have implications for reversing vision loss due to neurodegenerative disease or the aging process to improve the quality of life for millions of patients.
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Heightened concentrations of CO2 in inhaled air provoke temporary acidification of the brain, followed by compensatory hyperventilation and increased arousal/anxiety. These responses are likely to map a basic, latent general alarm/avoidance system that is largely shared across mammals, and are sources of individual differences. By showing paroxysmal respiratory and emotional responses to CO2 challenges, humans with panic and separation anxiety disorders lie at one extreme of the distribution for CO2 sensitivity. ⋯ Advantages of modeling CO2 sensitivity in rodents include non-inferential measurements (e.g. respiratory readouts) as proxies for human conditions, unbiased investigation of gene-environment interplays, and flexible availability of tissues for mechanistic studies. Data in humans and animals such as those reported in this issue of Neuroscience begin to reveal that CO2-driven behavioral responses stem from anatomo-physiological systems that are relatively separated from those subserving general dispositions to anxiety. This supports the notion that sensitivity to suffocative stimuli and ensuing human panic are significantly independent from trait/cognitive anxiety, and corroborates newer conceptualizations that distinguish between fear and anxiety circuitries.