Neuroscience
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Spastin is a microtubule-severing enzyme encoded by SPAST, which is broadly expressed in various cell types originated from multiple organs. Even though SPAST is well known as a regulator of the axon growth and arborization in neurons and a genetic factor of hereditary spastic paraplegia, it also takes part in a wide range of other cellular functions including the regulation of cell division and proliferation. In this study, we investigated a novel biological role of spastin in developing brain using Spast deficient mouse embryonic neural stem cells (NSCs) and perinatal mouse brain. ⋯ Using Spast shRNA treated NSCs and mouse brain, we showed that Spast deficiency leads to decrease of NSC proliferation and neuronal lineage differentiation. Finally, we found that spastin controls NSC proliferation by regulating microtubule dynamics in primary cilia. Collectively, these data demonstrate that spastin controls brain development by the regulation of NSC functions at early developmental stages.
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Elevated blood serotonin in perinatal development is the most consistent neurochemical finding reported in Autism Spectrum Disorder (ASD), and has been implicated in the pathogenesis of the disorder. Accordingly, pre- and postnatal administration of the non-selective serotonin agonist, 5-methoxytryptamine (5-MT), is hypothesized as a model of developmental hyperserotonemia (DHS) to investigate the behavioral and morphological implications in ASD. Our previous study, examining the effects of DHS, found significant neuroanatomical changes in the dendritic architecture and connectivity of neurons in the dentate nucleus of the cerebellum. ⋯ While results did not show a change in the overall volume of the thalamus, when grouped by estimated total brain volume, the mean thalamic volume was significantly reduced in the DHS group relative to controls. Additionally, significant reductions in cell numbers, density and distribution were observed in subdivisions of the principle nuclei including the ventral anterior, ventral lateral, ventral posterolateral, and ventral posteromedial nuclei. Alterations in these areas and their reciprocal connections throughout the brain may effect neuronal organization and be implicated in the neuropathological and behavioral changes observed in ASD.
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Pathological accumulation of tau protein in brain cells is the hallmark of a group of neurodegenerative diseases called tauopathies. Accumulation of tau protein begins years before the onset of symptoms, which include deficits in cognition, behavior and movement. The pre-symptomatic phase of tauopathy may be the best time to deliver disease-modifying treatments, but this is only possible if prognostic, pre-symptomatic biomarkers are identified. ⋯ Down-regulation of these microRNAs persisted at 53 weeks of age, when hTau mice exhibit cognitive deficits and advanced neuropathology. Bioinformatic analysis showed that these three microRNAs converge on pathways associated with neuronal signaling and phosphorylation of tau. Thus, these circulating microRNAs appear to reflect neuropathological change and are promising candidates in the development of biomarkers of pre-symptomatic tauopathy.
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Calcium overload has been reported to trigger neuronal death following stroke. Pseudoginsenoside-F11 (PF11), an ocotillol-type ginsenoside with various neuroprotective activities, has displayed therapeutic efficacy against permanent ischemic stroke. The present study examined the protective potential of PF11 in rats subjected to 2-h transient middle cerebral artery occlusion (tMCAO) and in cultured primary cortical neuron (PCN) exposed to oxygen-glucose deprivation/reoxygenation (OGD/R). ⋯ Furthermore, in vitro investigations showed PF11 increased cell viability, reduced neurites decline, restored ATP level and decreased calcium content in cultured PCN under OGD/R. Moreover, PF11 alleviated ERS, reversed the diminished levels of NMDA-2B subunit, postsynaptic density protein 95 and neuronal nitric oxide synthase both in vivo and in vitro. Our study indicates that PF11 produced neuroprotection and improved long-term outcomes while repressing calcium overload in model of transient focal ischemia, suggesting that PF11 might be a considerable candidate for stroke treatment.
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Astrocytes regulate extracellular glutamate homeostasis in the central nervous system through the Na+-dependent glutamate transporters glutamate transporter-1 (GLT-1) and glutamate aspartate transporter (GLAST). Impaired astrocyte glutamate uptake could contribute to the development of epilepsy but the regulation of glutamate transporters in epilepsy is not well understood. In this study, we investigate the expression of GLT-1 and GLAST in the mouse intrahippocampal kainic acid (IHKA) model of temporal lobe epilepsy (TLE). ⋯ GLAST immunoreactivity was increased in specific layers at 1 and 3 days post-IHKA in the ipsilateral hippocampus. GLAST synaptosomal protein levels were significantly elevated at 30 days compared to 7 days post-IHKA in the ipsilateral hippocampus. Our findings suggest that astrocytic glutamate transporter dysregulation could contribute to the development of epilepsy.