Brain research
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Neurotrophins participate in regulating the survival, differentiation, and target innervation of many neurons, mediated by high-affinity Trk and low-affinity p75 receptors. In the cochlea, spiral ganglion (SG) neuron survival is strongly dependent upon neurotrophic input, including brain-derived neurotrophic factor (BDNF), which increases the number of neurite outgrowth in neonatal rat SG in vitro. Less is known about signal transduction pathways linking the activation of neurotrophin receptors to SG neuron nuclei. ⋯ However, the identification of p38 and JNK involvement is entirely novel. The results suggest that neurotrophins can exert opposing effects on SG neurons, the balance of competing signals influencing the generation of neurites. This competition could provide a potential mechanism for the control of neurite number during development.
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Although previous researches indicated that heme oxygenase-1 (HO-1) plays a conspicuous role in neuronal injury induced by reperfusion following the brain ischemia, reasonable mechanisms for the role of HO-1 are not clear. In this work, we investigated whether HO-1 was involved in the regulation of the c-Jun N-terminal kinase (JNK) signaling pathway and neuronal cell injury induced by the brain ischemia followed by reperfusion. Cobaltic protoporphyrin (CoPP), an activator of HO-1, was administrated to induce the overexpression of HO-1 by intracerebroventricular infusion 20 min before ischemia. ⋯ Furthermore, pretreatment with CoPP significantly increased the survival of neurons after 5 days of reperfusion. In contrast, all of the above effects of CoPP were reversed by zinc protoporphyrin (ZnPP), a selective inhibitor of HO-1. Our results suggested that HO-1 could protect neurons against brain ischemic injury by downregulating the JNK signaling pathway through the MLK3-MKK7-JNK3 signaling module.
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The role of satellite glial cells (SGCs) of sensory ganglia in chronic pain begins to receive interest. The present study aims to investigate the contribution of SGC activation to the development of neuropathic pain. A neuropathic pain model was established by lumbar 5 spinal nerve ligation (SNL), and glial fibrillary acidic protein (GFAP) was used as a marker of SGC activation. ⋯ Continuous infusion of fluorocitrate, a glial metabolism inhibitor, to the affected DRG via mini-osmotic pump for 7d significantly alleviated mechanical allodynia at day 7. These results suggest that SGCs in the DRG were activated after SNL. SGC activation contributed to the early maintenance of neuropathic pain.
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Activation of glial cells and the intracellular ERK signaling pathway plays an important role in the development and maintenance of neuropathic pain. As well as neurons, glial cell membranes also express α₂-adrenergic receptors, but the effects of selective activation of these receptors on glial cell activation induced by neuropathic pain have yet to be clarified. We investigated the effects of intraperitoneal (IP) injections of tolerable doses of dexmedetomidine (DEX), a highly selective agonist of α₂-adrenergic receptors, on activation of spinal dorsal root glial cells and the intracellular ERK signaling pathway induced by neuropathic pain. ⋯ In addition, DEX 20 μg/kg for 14 days and 40 μg/kg for 7 days also significantly inhibited PSNL-induced activation of pERK in the spinal dorsal horn. Thus, repeated IP injections of DEX can markedly relieve the hyperalgesia of neuropathic pain in rats. The analgesic effect of DEX may be attributed to its inhibition of glial cell hypertrophy in the spinal dorsal horn and activation of the intracellular ERK signaling pathway.
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Noise exposure has been characterized as a stressor, and its non-auditory effects on the central nervous system have been established both epidemiologically and experimentally. Little is known about the impact of impulse noise on the brain, however. In this study, we examined the effects of impulse noise stress on spatial learning and memory and on associated changes in the hippocampus. ⋯ Impulse noise stress also caused a significant increase in NMDAR 2B subunit (NR2B) expression and a two-phase increase in tau phosphorylation in hippocampus. Immunohistochemistry confirmed tau hyperphosphorylation in hippocampus that was most prominent in the dentate gyrus (DG) and CA1 region. These findings demonstrate that impulse noise stress impairs early spatial memory, possibly by disrupting Glu-NMDAR signaling and triggering aberrant tau hyperphosphorylation in hippocampus.