Neuroscience
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Aquaporins (AQPs) play critical physiological roles in water balance in the central nervous system (CNS). Aquaporin-4 (AQP4), the principal aquaporin expressed in the CNS, has been implicated in the processing of sensory and pain transmission. Akt signaling is also involved in pain mediation, such as neuroinflammatory pain and bone cancer pain. ⋯ Furthermore, Akt blockade with MK2206 alleviated NP in the early and late phases after SNL. These results elucidate the mechanisms involved in the roles of Akt/AQP4 signaling in the development and maintenance of NP. AQP4 is likely to be a novel therapeutic target for NP management.
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Our previous study showed that electroacupuncture (EA) pretreatment elicited protective effect on cerebral ischemia-reperfusion injury (CIRI) in rats, at least partly, which was associated with transient receptor potential vanilloid 1 (TRPV1)-regulated anti-oxidant stress and anti-inflammation. In this study, we further investigated the possible contribution of TRPV1-mediated anti-apoptosis in EA pretreatment-evoked neuroprotection in CIRI. After EA pretreatment at Baihui (GV20), bilateral Shenshu (BL23) and Sanyinjiao (SP6) acupoints, transient focal cerebral ischemia was induced by middle cerebral artery occlusion (MCAO) for 2 h followed by reperfusion for 6 h in rats. ⋯ The presented data showed that EA pretreatment significantly reduced infarct volume, relieved nerve cell injury, decreased the expression of pro-apoptotic proteins Bax and cleaved caspase-3, increased the level of anti-apoptotic protein Bcl-2, inhibited NF-κB (p65) transcriptional activity, and curbed TRPV1 expression in MCAO rats. By contrast, enhancement of TRPV1 expression accompanying capsaicin application, the specific TRPV1 agonists, markedly accelerated nerve cell damage, aggravated neuronal apoptosis, prompted nuclear translocation of NF-κB (p65), resulting in the reversion of EA pretreatment-evoked neuroprotective effect in MCAO rats. Thus, we conclude that EA pretreatment-induced downregulation of neuronal TRPV1 expression plays an anti-apoptosis role through inhibiting NF-κB signaling pathway, thereby protecting MCAO rats from cerebral ischemia-reperfusion injury.
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The cerebellum has been shown to be involved in temporal information processing. We recently demonstrated that neurons in the cerebellar dentate nucleus exhibited periodic activity predicting stimulus timing when monkeys attempted to detect a single omission of isochronous repetitive visual stimulus. In this study, we assessed the relative contribution of signals from Purkinje cells and mossy and climbing fibers to the periodic activity by comparing single neuronal firing before and during local infusion of GABA or glutamate receptor antagonists (gabazine or a mixture of 1,2,3,4-tetrahydro-6-nitro-2,3-dioxo-benzo[f]quinoxaline-7-sulfonamide hydrate (NBQX) and (±)-3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP)). ⋯ We also found that the variation of baseline activity decreased during gabazine application but sometimes increased during the blockade of glutamate receptors. These changes were not observed during prolonged recording without drug administration. These results suggest that the predictive neuronal activity in the dentate nucleus may mainly attribute to the inputs from the cerebellar cortex, while the signals from both mossy fibers and Purkinje cells may play a role in setting the level and variance of baseline activity during the task.
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The electrophysiological properties of undifferentiated SH-SY5Y cells were examined during cultures prolonged even to 20 days by measuring the passive and active membrane properties at 5 days interval, as well as the spontaneous spiking activity. The results showed that culturing this cell for long time affected not only membrane shape but also their electrophysiological properties. ⋯ These modifications would synergically contribute to the bioelectrical conversion of these cells and could be part of a more complex machinery with which the tumoral cell would regulate its survival advantage and resilience. Understanding these processes could add a new clue to the exploitation of this preclinical human neuronal model.