Neuroscience
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Intracerebral hemorrhage (ICH) is a hemorrhagic stroke with a high mortality and disability rate. Neurological impairment after ICH is closely associated with neuronal axon damage. Serine/threonine-protein kinase p21 activated kinase 1 (PAK1) participates in cytoskeletal remodeling and regulates the F-actin and G-actin ratio in neuronal axons, but the function of PAK1 after ICH remains unclear. ⋯ Knockdown of PAK1 increased the live/dead cell ratio and promoted neurons survival. Our study showed that PAK1 is involved in ICH early secondary brain injury by affecting F-actin/G-actin ratio through the PAK1/LIMK1/cofilin pathway. PAK1 may be an essential target for early secondary brain injury intervention after ICH.
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Glycogen synthase kinase-3β (GSK-3β) is a highly expressed kinase in the brain, where it has an important role in synaptic plasticity. Aberrant activity of GSK-3β leads to synaptic dysfunction which results in the development of several neuropsychiatric and neurological diseases. Notably, overexpression of constitutively active form of GSK-3β (GSK-3β[S9A]) in mice recapitulates the cognitive and structural defects characteristic for neurological and psychiatric disorders. ⋯ Next, characterization of miR-221* function in primary hippocampal cell culture transfected by miR-221* inhibitor, showed no structural changes in dendritic spine shape and density. Using electrophysiological methods, we found that downregulation of miR-221* increases excitatory synaptic transmission in hippocampal neurons, probably via postsynaptic mechanisms. Thus, our data reveal potential mechanism by which GSK-3β and miRNAs might regulate synaptic function and therefore also synaptic plasticity.
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Diabetic neuropathy is one of the most common complications in patients with diabetes and leads to cognitive impairment. It is suggested that protracted hyperglycemia is the main trigger of cognitive deficits in diabetes and causes hippocampal abnormalities. Rapamycin, an inhibitor of mammalian target of rapamycin complex 1 (mTORC1), can significantly ameliorate cognitive deficits in neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease and Huntington disease. ⋯ However, rapamycin pre-treatment reversed the changes induced by high glucose. Moreover, we demonstrated that rapamycin pre-treatment reversed the down-regulation of postsynaptic density protein 95 (PSD-95) expression caused by high glucose. Therefore, pre-treatment with rapamycin could ameliorate high glucose-induced alteration of synaptic transmission in the hippocampal dentate gyrus.
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Perioperative neurocognitive disorder (PND) is a serious nervous system complication characterized by progressive cognitive impairment, especially in geriatric population. However, the neuropathogenesis of PND is complex, and there are no approved disease-modifying therapeutic options. Mitochondrial dysfunction has been demonstrated to contribute to the occurrence and development of PND. ⋯ Our results suggested that tNIR light was an effective treatment of PND through PBMT effect, accompanied by synaptic and neuronal improvement. The improvement of mitochondrial dysfunction mediated by SIRT1/PGC-1α signaling pathway might participate in this process. Those findings might provide a novel and noninvasive therapeutic target for PND.
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Vestibular schwannoma (VS) is a benign, slow-growing neoplasm, which is an important cause of sensorineural hearing loss. Circular RNAs (circRNAs) have been widely reported to be dysregulated and participate in multiple biological processes of human diseases. However, roles of most circRNAs still remain explored. ⋯ Additionally, results of mechanism assays demonstrated that circ_0001665 could function as a sponge of microRNA-302a-3p (miR-302a-3p) to enhance Adam9 expression and to activate EGFR signaling pathway in VS cells. Eventually, it was indicated in rescue assays that circ_0001665 expedited proliferation and restrained apoptosis of VS cells via modulation on miR-302a-3p/Adam9. Collectively, our study identified a novel perspective for exploration into molecular mechanisms in VS.