Neuroscience
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As an adult-onset neurodegenerative disease, amyotrophic lateral sclerosis (ALS) results in progressive muscular atrophy and paralysis. However, the mechanism of ALS has not yet been elucidated, and no cure has been found. Research has revealed that a mutation of the Cu/Zn superoxide dismutase (SOD1) gene is linked to familial ALS and that potential sex discrepancies exist in ALS incidence. ⋯ This protective effect occurred through anti-apoptotic pathways related to estrogen receptor-alpha (ER-α) activation. Meanwhile, knockdown of aromatase with Cyp19a1 ShRNA plasmid transfection reduced cell proliferation, increased cell damage, promoted apoptosis, and decreased ER-α expression in hSOD1-G93A cells, and the induced apoptotic effects could be reversed by estradiol (E2). In brief, the results of our study suggest that aromatase plays a neuroprotective role against apoptosis in hSOD1-G93A cells by activating ER-α and may become a new intervention target for ALS treatment.
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We study the transition in the functional networks that characterize the human brains' conscious-state to an unconscious subliminal state of perception by using k-core percolation. We find that the most inner core (i.e., the most connected kernel) of the conscious-state functional network corresponds to areas which remain functionally active when the brain transitions from the conscious-state to the subliminal-state. ⋯ Thus, the inner core and most robust component of the conscious brain corresponds to the unconscious subliminal state. This finding imposes constraints to theoretical models of consciousness, in that the location of the core of the functional brain network is in the unconscious part of the brain rather than in the conscious state as previously thought.
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Silent angina is a critical phenomenon in the clinic and is more commonly associated with women patients suffering from myocardial ischemia. Its underlying cause remains mysterious in medicine. With our recent discovery of female-specific Ah-type baroreceptor neurons (BRNs), we hypothesize that cardiac analgesia is due to the direct activation of Ah-type BRNs by elevated levels of circulating serotonin (5-HT) myocardial infarction (MI) patients. ⋯ Although the tail-flick reflex and mean arterial pressure were dramatically reduced in female MI rats with elevated serum 5-HT, intrapericardial capsaicin-evoked muscular discharges were significantly inhibited in comparing with those of males, which were mimicked by microinjection of 5-HT or SR57227A into the nodose. Ah-type BRNs displayed robust inward currents at lower concentrations of 5-HT than the C-type or the A-type, with significantly increased expression and cellular distribution of 5-HT3AR but not 5-HT3BR compared to the A- and C-types. Activation of 5-HT3AR in Ah-type BRNs by 5-HT contributes significantly to cardiac analgesia, which may suggest the pathogenic condition that silent angina occurs mainly in female patients.
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The perirhinal (PER) - lateral entorhinal (LEC) network plays a pivotal role in the information transfer between the neocortex and the hippocampus. Anatomical studies have shown that the connectivity is organized bi-directionally: the superficial layers consist of projections running from the neocortex via the PER-LEC network to the hippocampus while the deep layers form the output pathway back to the neocortex. Although these pathways are characterized anatomically, the functional organization of the superficial and deep connections in the PER-LEC network remains to be revealed. ⋯ We performed paired recordings in superficial layer principal neurons and parvalbumin (PV) expressing interneurons to address how this window of opportunity for spiking is affected in superficial principal neurons. The PV interneuron population initiated inhibition at a very consistent timing with increasing stimulus intensity, whereas the excitation temporally shifted to ensure action potential firing. These data indicate that superficial principal neurons can transmit cortical synaptic input through the PER-LEC network because these neurons have a favorable window of opportunity for spiking in contrast to deep neurons.
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Angiopoietin (Ang) is an angiogenic factor, but its neuroprotective and neurotrophic effects have recently come to light. Ang exerts neuroprotective effects by inhibiting neuronal apoptosis, protecting the blood-brain/blood-spinal cord barrier, reducing inflammation and promoting neovascularization. ⋯ In addition, Ang and vascular endothelial growth factor (VEGF) are known to interact in blood vessels in the nervous system and the combination of Ang and VEGF can mitigate the negative effects of VEGF, such as inflammation and local edema. These data indicated that Ang is a novel neuroprotective/neurotrophic factor, which may become a new tool for the treatment of nerve injury.