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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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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In hypertensive retinopathy, the retinal damage due to high blood pressure is accompanied by increased expression of Glial Fibrillary Acidic Protein (GFAP), which indicates a role of neuroinflammatory processes in such a retinopathy. Proteins belonging to the Rho GTPase family, particularly Rac1, are involved in the activation of Müller glia and in the progression of photoreceptor degeneration, and may thus represent a novel candidate for therapeutic intervention following central nervous system inflammation. ⋯ Furthermore, such functional improvement is accompanied by a reduction of Rac1 activity and retinal GFAP expression. Our results suggest that Rac1 inhibition through CNF1 topical administration may represent a new strategy to target retinal gliosis.
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Response inhibition is a central aspect of cognitive control. Usually, response inhibition is examined using information from a single sensory modality. Yet, evidence suggests that conflicts between information from different modalities affect response inhibition. ⋯ This also explains why less intense braking processes (reflected by IFG activity) are still able to maintain a reasonable response inhibition performance level. It can be concluded that the tactile and visual domains do not only differ in regard to their efficiency to trigger response inhibition processes but also in their susceptibility to interference while informing inhibitory control. Clinical implications are discussed.