Neuroscience
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DFNA2 is a progressive deafness caused by mutations in the voltage-activated potassium channel KCNQ4. Hearing loss develops with age from a mild increase in the hearing threshold to profound deafness. Studies using transgenic mice for Kcnq4 expressed in a mixed background demonstrated the implication of outer hair cells at the initial phase. ⋯ We also established that outer hair cell loss kinetics slowed down from basal to apical regions correlating with KCNQ4 expression pattern determined in wild-type mice. Our findings indicate that KCNQ4 plays differential roles in each cochlear cell-type impacting in their survival ability. Inner hair cell and spiral ganglion neuron death generates severe hearing loss that could be associated with the last phase of DFNA2.
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Transient ischemic attack (TIA) represents brief neurological dysfunction of vascular origin without detectable infarction. Despite major clinical relevance characterization of post-TIA molecular changes using appropriate experimental model is lacking and no therapeutic agent has been established yet. Neurosteroid dehydroepiandrosterone (DHEA) arose as one of the candidates for cerebral ischemia treatment but its effects on TIA-like condition remain unknown. ⋯ DHEA had no effects in physiological conditions, while increase of Bax/Bcl2 ratio and dissipation of mitochondrial membrane potential in treated I/R group suggested DHEA-mediated exacerbation of post-ischemic changes that might lead to pro-apoptotic events in HIP. Interestingly, DHEA restored I/R-induced NO to the control level in PFC. Obtained results indicated that I/R may serve as an appropriate model for investigation of molecular changes and treatment outcome following mild ischemic conditions such as TIA.
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Neurobrucellosis, which is the most morbid form of brucellosis disease, presents with inflammatory signs and symptoms. Recent experimental evidence clearly indicates that deregulation of astrocytes and microglia caused by Brucella infection creates a microenvironment in the central nervous system (CNS) in which secretion of pro-inflammatory mediators lead to destabilization of the glial structure, the damage of the blood brain barrier (BBB) and neuronal demise. This review of Brucella interactions with cells of the CNS and the BBB is intended to present recent immunological findings that can explain, at least in part, the basis for the inflammatory pathogenesis of the nervous system that takes place upon Brucella infection.
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The present study investigated how pain appraisals from other individuals modulated self-pain anticipation and perception. Appraisals of pain intensity from 10 other individuals were presented before the participants received identical electrical pain stimulation themselves. In reality, the presented other's pain appraisals, with either low or high in mean and variance, were generated by the experimenter, and were randomly paired with the subsequent electrical stimulation at either low or high intensity. ⋯ In contrast, when the mean was high, the higher variance enhanced sensorimotor α-oscillations and suppressed subsequent pain perception. These results demonstrated that others' pain appraisals can modulate both of the anticipation and perception of first-hand pain. It also suggested that the top-down modulation of others' pain appraisals on pain perception could be partially driven by the different brain states during the anticipation stage, as captured by the prestimulus sensorimotor α-oscillations.
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γ-Synuclein (γ-syn) is expressed by astrocytes in the human nervous system, and increased extracellularly in the brain and cerebrospinal fluid of individuals diagnosed with Alzheimer's disease. Upregulation of γ-syn also coincides with proliferation of glioblastomas and other cancers. In order to better understand regulation and function of extracellular γ-syn, primary human cortical astrocytes were treated with γ-syn conditioned media at various physiological concentrations (50, 100, 150 nM) after cell synchronization. ⋯ Further analysis of cell cycle markers with immunocytochemistry of BrdU and Ki67 after treatment with 100 nM γ-syn confirmed increased initial cell proliferation and decreased non-proliferating cells. Western blot analysis demonstrated increased γ-syn levels after 100 nM treatment at 24 and 48 h, and increased pro-BDNF, mature BDNF and cell viability at 48 h. The results demonstrate that γ-syn internalization by human cortical astrocytes causes upregulation of the cell cycle, followed by subsequent BDNF expression and release.