Neuroscience
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Myelinated Ah-type vagal ganglion neurons (VGNs) were specific subpopulation in adult females, rather than neonate and key players in sexual dimorphism in baroreflex afferent function and closely associated with estrogen. However, the gender related development changes in Ah-type VGNs remains unknown. To quantify the developmental changes in ion channels overtime, the whole-cell patch-clamp technique was performed and three afferent fiber types of VGNs were identified upon electrophysiological/pharmacological validations. ⋯ The coordinated changes in the current density of certain ion channels may be the underlying mechanism of developmental changes in AP waveform and neuroexcitability. As expected, the coordinated change between the down-regulation of iberiotoxin-sensitive and up-regulation of 4-aminopyridine-sensitive K+ currents played a key role in shaping AP and neuroexcitability in Ah-types during development. Our results demonstrated that the myelinated Ah-type VGNs in males almost disappear at 4 weeks old where closes to adult and the correlative ion channel changes contribute to the sexual dimorphism in visceral afferent function.
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Unfolded protein response is a signaling cascade triggered by misfolded proteins in the endoplasmic reticulum. Heat shock protein H4 (HSPH4) and A5 (HSPA5) are two chaperoning proteins present within the organelle, which target misfolded peptides during prolonged stress conditions. Epileptogenic insults and epileptic seizures are a notable source of stress on cells. ⋯ This characterization of HSPA5 and HSPH4 expression provided extensive information regarding spatial and temporal alterations of the two proteins during SE-induced epileptogenesis and following epilepsy manifestations. Up-regulation of both proteins implies stress exerted on ER during these disease phases. Taken together suggest a differential impact of epileptogenesis on HSPA5 and HSPH4 expression and indicate them as a possible target for pharmacological modulation of unfolded protein response.
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Acceleration of cytoskeletal remodeling in regenerated axons is crucial for a fully functional recovery following peripheral nerve injury (PNI). Melatonin plays important roles in cell differentiation and protection of cytoskeleton stability, thus, the present study aimed to investigate whether melatonin can enhance neurite outgrowth and promote cytoskeletal remodeling in a PNI animal model and in differentiated neurons. End-to-side neurorrhaphy (ESN) rat model was used for assessing cytoskeletal rearrangement in regenerated axon. ⋯ Treatment with a melatonin receptor antagonist, luzindole, significantly suppressed melatonin receptors and β3-tubulin expression. Importantly, we found that melatonin treatment suppressed activation of calmodulin-dependent protein kinase II (CaMKII) in vitro and in vivo, suggesting that the β3-tubulin remodeling may occur via CaMKII-mediated Ca2+ signaling. These results suggested that melatonin may promote functional recovery after PNI by accelerating cytoskeletal remodeling through the melatonin receptor-dependent pathway.