Neuroscience
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Syntaxin-binding protein 1 (STXBP1, also known as Munc18-1) regulates exocytosis as a chaperone protein of Syntaxin1A. The haploinsufficiency of STXBP1 causes early infantile-onset developmental and epileptic encephalopathy, known as STXBP1 encephalopathy. Previously, we reported impaired cellular localization of Syntaxin1A in induced pluripotent stem cell-derived neurons from an STXBP1 encephalopathy patient harboring a nonsense mutation. ⋯ These proteins colocalized at the tip of the growth cone and axons in primary cultured hippocampal neurons. Furthermore, RNAi-mediated gene silencing in Neuro2a cells showed that STXBP1 and Myosin Va were required for membrane trafficking of Syntaxin1A. In conclusion, this study proposes a potential role of STXBP1 in the trafficking of the presynaptic protein Syntaxin1A to the plasma membrane in conjunction with Myosin Va.
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Cerebral ischemic reperfusion injury could emanate a cascade of events ensuing in neural death and severe neurobehavioural deficits. The currently available interventions have failed to target the multimodal, interlinked mechanisms that operate cerebral ischemia-induced damage and functional loss. So an integrative intervention has become a mandate to overcome the deleterious mechanisms involved in cerebral ischemic pathophysiology. ⋯ The BBB integrity was well preserved in the combination group when compared with the lesion and standalone groups. Moreover, the combined intervention reduced the level of pro-inflammatory cytokines TNFα, NFkB, IL1α, IL1-β, IL-6, CD68, COX-2, and mRNA expression of inflammatory genes IL1α, IL1-β, IL-6, IBA-1, and COX-2 effectively. In conclusion, the present study suggests that rMCAo induced neuroinflammation and neurobehavioural alterations were attenuated by intervention with a combination of Fucoidan and cerebrolysin; Further, Fucoidan and Cerebrolysin combination improved the ischemic tolerance level by promoting the proteins and genes that regulate the inflammatory cytokines and in aiding better recovery after ischemic reperfusion injury.
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Memories already consolidated when reactivated return to a labile state and can be modified, this process is known as reconsolidation. It is known the Wnt signaling pathways can modulate hippocampal synaptic plasticity as well as learning and memory. Yet, Wnt signaling pathways interact with NMDA (N-methyl-D-aspartate) receptors. ⋯ Moreover, the impairment induced by DKK1 was blocked by the administration of the agonist of the NMDA receptors glycine site, D-Serine, immediately and 2 h after reactivation session. We found that hippocampal canonical Wnt/β-catenin is necessary to the reconsolidation of CFC memory at least two hours after reactivation, while non-canonical Wnt/Ca2+ signaling pathway is not involved in this process and, that there is a link between Wnt/β-catenin signaling pathway and NMDA receptors. In view of this, this study provides new evidence regarding the neural mechanisms underlying contextual fear memory reconsolidation and contributes to provide a new possible target for the treatment of fear related disorders.
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Apolipoprotein E (apoE, protein; APOE, gene), divided into three alleles of E2, E3 and E4 in humans, is associated with the progression of white matter lesion load. However, mechanism evidence has not been reported regarding the APOE genotype in early white matter injury (WMI) under subarachnoid hemorrhage (SAH) conditions. In the present study, we investigated the effects of APOE gene polymorphisms, by constructing microglial APOE3 and APOE4-specific overexpression, on WMI and underlying mechanisms of microglia phagocytosis in a mice model of SAH. ⋯ The increased ROS and aggravating mitochondrial damage demonstrated that the damaging effects of APOE4 in SAH may be associated with microglial oxidative stress-dependent mitochondrial damage. Inhibiting mitochondrial oxidative stress by Mitoquinone (mitoQ) can enhance the phagocytic function of microglia. In conclusion, anti-oxidative stress and phagocytosis protection may serve as promising treatments in the management of SAH.
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Peripheral nerve injury (PNI) induces severe functional loss in extremities. Progressive denervation and atrophy occur in the muscles if the nerve repair is delayed for long periods of the time. To overcome these difficulties, detailed mechanisms should be determined for neuromuscular junction (NMJ) degeneration in target muscles after PNI and regeneration after nerve repair. ⋯ In addition, NMJ- and Schwann cell-related molecules showed high expression in the target muscle in the allograft model. These results suggest that Schwann cell migrating from the allograft might play a crucial role in nerve regeneration in the chronic phase after PNI. The relationship between the NMJ and Schwann cells should be further investigated in the target muscle.