Neuroscience
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Periventricular leukomalacia (PVL) is a severe type of white matter damage in premature infants and the most common cause of cerebral palsy. It is generally known to be caused by hypoxia and inflammation. Currently there is no effective treatment available, in part due to that the pathogenesis of the disease has not been well understood. ⋯ The electron microscopic images demonstrated that the microstructure of myelin structures was not significantly different between the wild-type and p38α MAPK CKO mice. In addition, oligodendrocyte degeneration in the corpus callosum white matter area was unaffected in the p38α MAPK CKO during and after the PVL induction. These data indicate that p38α MAPK in oligodendrocyte has minimal effect on myelination and oligodendrocyte survival in the mouse PVL model.
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Human spatial manipulation ability is sensitive to high-altitude (HA) environment. The present study aimed to investigate the electrophysiological basis of spatial manipulation ability on adult immigrants with long-term HA exposure using the mental rotation (MR) task and the ERP approach. Toward this end, we explored the MR effect in individuals who immigrated to HA areas for three years compared with individuals who lived in low altitude areas. ⋯ The ERP component analysis further indicated that the rotation-related negativity (RRN) amplitude was highly corresponding to the MR effect in each group, the RRN amplitude was significantly larger in the HA group than the low-altitude group related to each rotation angle condition. The brain topographical map further showed that only the right hemisphere regions instead of the bilateral hemisphere regions involved into the MR effect in the HA group, which was different to the low-altitude group. Together, these findings might collectively suggest that the mental resource was insufficient as a result of HA exposure which can be reflected on the RRN amplitude, which may help understanding the neural basis of spatial ability change from the long-term HA exposure.
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The Na+/K+/Cl- cotransporter-1 (NKCC1) and the K+/Cl- cotransporter-2 (KCC2) set the transmembrane Cl- gradient in the brain, and are implicated in epileptogenesis. We studied the postnatal distribution of NKCC1 and KCC2 in wild-type (WT) mice, and in a mouse model of sleep-related epilepsy, carrying the mutant β2-V287L subunit of the nicotinic acetylcholine receptor (nAChR). In WT neocortex, immunohistochemistry showed a wide distribution of NKCC1 in neurons and astrocytes. ⋯ However, KCC2 expression decreased by P60 in the reticular nucleus, and more so in mice expressing β2-V287L. Therefore, a complex regulatory interplay occurs between heteromeric nAChRs and KCC2 in postnatal forebrain. The pathogenetic effect of β2-V287L may depend on altered KCC2 amounts in PFC during synaptogenesis, as well as in mature thalamocortical circuits.
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Perampanel (PER), a noncompetitive α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptor antagonist, clinically used for seizure control, has been reported to exert neuroprotective effects in experimental models of neurodegenerative diseases. However, few studies have investigated the therapeutic effects of PER in brain injury including stroke. Our aim was to investigate the neuroprotective potential of PER using a rat transient middle cerebral artery occlusion (MCAO) model. ⋯ In addition, post-stroke secondary neuronal damage and cognitive impairments, using the Y-maze test, were assessed 30 days after MCAO. PER significantly improved spatial working memory, which was accompanied by hippocampal CA1 neuronal loss and cortical thinning, compared with vehicle. These results indicate that PER attenuates infarct volumes and motor function deficits possibly through its anti-inflammatory, antioxidant, and anti-apoptotic activities, mediated via activation of phosphatidylinositol 3-kinase (PI3K)/Akt pathways in the acute ischemic phase, and further ameliorates post-stroke cognitive impairments via the suppression of secondary neuronal damage in the chronic ischemic phase.
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P2X2 receptors are ligand-gated cation channels activated by extracellular ATP that modulate neural transmission in various neuronal systems. Although the function and distribution of P2X2 receptors in the cochlea portion of the inner ear are well established, their physiological role in the vestibular portion is still not understood. Therefore, we investigated P2X2 receptor localization in the peripheral vestibular portion, and assessed their physiological function in vivo using P2X2 receptor knock out (P2X2-KO) mice. ⋯ VOR gain in P2X2-KO mice was significantly reduced, with no decrease in the optokinetic response. In conclusion, we showed that P2X2 receptors are mainly localized in the supporting cells of the vestibular inner ear, and the loss of P2X2 receptors causes mild vestibular dysfunction. Taken together, our findings suggest that the P2X2 receptor plays a modulatory role in vestibular function.