Neuroscience
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The comparative roles of the human amygdala and orbitofrontal cortex in emotional processing are under substantial debate, supported prominently by invasive primate studies. Noninvasive studies in humans are restricted by the limitations of electro- and magneto-encephalographic methods, which are hampered by the closed-field architecture and deep location of these structures. Here we employ whole-brain functional magnetic resonance imaging at an effective sampling rate of 300 ms to define the latency of enhanced blood oxygen level dependent (BOLD) contrast within structures activated by emotionally evocative relative to neutral scenes, in an effort to assess the hypothesized primacy of amygdala-inferotemporal co-activity in human emotional perception, relative to orbitofrontal cortex. ⋯ Subcortical structures including the amygdala, locus coeruleus, and basal forebrain also showed reliably increased activity during emotional scene perception. The latency at which emotional BOLD signal enhancement varied considerably across structures, ranging from 2 to 6 seconds after scene onset. Though coarse, the spatiotemporal pattern of emotion-enhanced activity identified here is consistent with the idea that the amygdala and inferior temporal fusiform gyrus are the first regions to discriminate scene emotionality, which may then distribute this categorical information to other cortical and subcortical structures.
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Exploring sexual dimorphisms in the brain morphology is important for their impact and therapeutic implications for several neurological diseases. The hypothesis that sex could influence the transcriptome of brain cells could be the basis regarding the different response to cognitive decline identified in men and women. In this paper, we analyzed several prefrontal cortices (PFC) microarrays datasets of young/middle-aged healthy subjects and then Alzheimer's disease (AD) patients, according to the sex. ⋯ In addition, the sex-matched analysis of transcriptome identified a convergent molecular signature in men and women AD patients. Furthermore, the WPSEG belonging to CNS cells in PFC of healthy middle-aged subjects was correlated to AD profiles according to the sex. Since our results, it is possible to conclude that during the aging the PFC' cells adopt transcriptional strategies sex-dependent that could potentially control the development of neurodegenerative diseases.
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The over-activation of N-methyl-D-aspartate receptors (NMDARs) is the main cause of neuronal death in brain ischemia. Both the NMDAR and the Acid-sensing ion channel 1a (ASIC1a) are present in the postsynaptic membrane of the central nervous system (CNS) and participate in physiological and pathological processes. However, the specific role played by ASIC1a in these processes remains elusive. ⋯ Furthermore, brain infarct sizes were reduced by a greater degree in older mice compared to younger ones when ASIC1a activity was suppressed. These data suggest that ASIC1a activity selectively enhances the function of triheteromeric NMDARs and exacerbates ischemic neuronal death especially in older animal brains. We propose ASIC1a as a novel therapeutic target for preventing and reducing the detrimental effect of brain ischemia in humans.
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Profiling the Gene Expression and DNA Methylation in the Mouse Brain after Ischemic Preconditioning.
Ischemic preconditioning (IPC) is a phenomenon in which a short-term sublethal ischemic exposure induces tolerance to a subsequent lethal ischemic insult; however, the detailed mechanism underlying IPC-induced neuroprotection remains obscure. Here, we applied middle cerebral artery occlusion, a preconditioning ischemic insult mouse model, to investigate the molecular mechanism underlying cerebral IPC. RNA sequencing and whole-genome bisulfite sequencing were performed to explore the gene expression profile and DNA methylation changes after cerebral IPC treatment. ⋯ The involvement of several genes in IPC-induced neuroprotection was first reported. Genes induced by IPC, including Arid5a, Nptx2 and Stc2, demonstrated a neuroprotective effect against oxygen-glucose deprivation induced neurotoxicity in vitro. Thus, our findings provide new insights into IPC signaling pathways and offer a novel therapeutic strategy towards stroke.
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Valproic acid (VPA) is widely used in the treatment of epilepsy. However, VPA has been revealed to impair memory of both humans and animals. The adverse effects of VPA are associated with reductions in hippocampal neurogenesis and memory. ⋯ It is noteworthy that rats receiving melatonin alone showed a significant diversity of proliferation, survival and immature neurons compared to the control rats. These findings suggest that melatonin is able to prevent the spatial and non-spatial memory impairments and a reduction in hippocampal neurogenesis simultaneously induced by VPA. Our results provide a feasible way to prevent this loss using melatonin.