Neuroscience
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Neonatal inflammation induces long-term effects on brain function. We investigated the effects of systematic neonatal inflammation using lipopolysaccharide (LPS) injection at postnatal day 3 (P3) and P5 in a mouse model of spatial memory capacity measured using a Morris water maze (MWM) task in adulthood. Subsequently, we assessed histone acetylation and immediate-early response gene expression (c-Fos and brain-derived neurotrophic factor) in the hippocampus in response to MWM acquisition training. ⋯ TSA also increased c-Fos gene expression underlying synaptic plasticity and memory formation, and consequently rescued impaired spatial cognitive function. These results indicate that the dysregulation of H4K12 acetylation during the ongoing process of memory formation plays a key role in the spatial cognitive impairment associated with a neonatal LPS challenge. The histone deacetylase inhibitor TSA exhibits therapeutic potential for treating cognitive impairment induced by neonatal inflammation, by means of improving hippocampal histone acetylation and downstream c-Fos gene expression in response to a learning task.
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Reactive oxygen species (ROS) modulate the growth of neural stem/precursor cells (NS/PCs) and participate in hippocampus-associated learning and memory. However, the origin of these regulatory ROS in NS/PCs is not fully understood. In the present study, we found that Nox4, a ROS-producing NADPH oxidase family protein, is expressed in primary cultured NS/PCs and in those of the adult mouse brain. ⋯ Although pathological and functional damages in the hippocampus induced by the neurotoxin trimethyltin were not significantly different between wild-type and Nox4-/- mice, the post-injury reactive proliferation of NS/PCs and neurogenesis in the subgranular zone (SGZ) of the dentate gyrus were significantly impaired in Nox4-/- animals. Restoration from the trimethyltin-induced impairment in recognition and spatial working memory was also significantly attenuated in Nox4-/- mice. Collectively, our findings suggest that Nox4 participates in NS/PC proliferation and neurogenesis in the hippocampus following injury, thereby helping to restore memory function.
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Many studies have implicated hippocampal dysregulation in the pathophysiology of alcohol use disorder (AUD). However, over the past twenty years, a growing body of evidence has revealed distinct functional roles of the dorsal (dHC) and ventral (vHC) hippocampal subregions, with the dHC being primarily involved in spatial learning and memory and the vHC regulating anxiety- and depressive-like behaviors. Notably, to our knowledge, no rodent studies have examined the effects of chronic ethanol exposure on synaptic transmission along the dorsal/ventral axis. ⋯ Extracellular recordings revealed marked CIE-associated increases in synaptic excitation in the CA1 region that were exclusively restricted to the ventral domain of the hippocampus. Western blot analysis of synaptoneurosomal fractions revealed that the expression of two proteins that regulate synaptic strength, GluA2 and SK2, were dysregulated in the vHC, but not the dHC, following CIE. Together, these findings suggest that the ventral CA1 region may be particularly sensitive to the maladaptive effects of chronic ethanol exposure and provide new insight into some of the neural substrates that may contribute to the negative affective state that develops during withdrawal.
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Dravet syndrome (DS) is a disease that is primarily caused by the inactivation of the SCN1A-encoded voltage-gated sodium channel alpha subunit (Nav1.1). In this study, we constructed an SCN1A gene knockout model using CRISPR/Cas9 genome editing technology to deprive the Nav1.1 function in vitro. ⋯ We also noticed changes in the spliceosome, decreased glycolytic capacity, disturbances in calcium signaling pathways, and changes in the potassium, sodium, chloride, and calcium plasma channels after SCN1A knockout. In this study, we have been the first time to discover these changes and summarize them here and hope it would provide some clue for the study of Nav1.1 in the nervous system.
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Stroke is a leading cause of mortality and serious disability worldwide with limited treatment options. Angiogenesis has been reported to be involved in post-stroke recovery. Although the molecular mechanisms that regulate angiogenesis remain ambiguous, microRNAs have emerged as effective regulators of angiogenesis, involved in neurological function outcome. ⋯ Enhanced angiogenesis in ischemic boundary zone (IBZ) was observed, and the neurological outcome during the entire study period was improved. The number of phosphate-AMPKα2+ cells that co-expressed endothelial cell marker CD31 was significantly increased. Taken together, the present study demonstrated that downregulated miRNA-27b promoted recovery after ischemic stroke via AMPK stimulus.