Neuroscience
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This study aimed to elucidate the mechanism for alteration of m6A RNA modification in cerebral ischemia/reperfusion(I/R) injury and identify novel therapeutic targets. A rat cerebral I/R injury model was established by middle cerebral artery occlusion (MCAO) followed by reperfusion. Changes in m6A RNA modification were evaluated by colorimetric quantification. ⋯ Notably, miR-155 overexpression blunted FTO's protective effect against cerebral I/R injury. We propose that downregulation of FTO expression contributes to increased m6A RNA modification in cerebral I/R injury. FTO overexpression reverses increased total m6A RNA modification and exerts a protective effect against cerebral I/R injury via downregulating m6A modification of pri-miR-155 to inhibit its maturation process.
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Epilepsy is a disabling and drug-refractory neurological disorder. Long non-coding RNAs (lncRNAs) play a vital role in neuronal function and central nervous system development. This study aimed to explore the regulatory mechanism of lncRNA five prime to Xist (FTX) in cell ferroptosis following epilepsy to provide a theoretical foundation for epilepsy management. ⋯ FTX regulated GABPB1 expression by targeting miR-142-5p. In conclusion, FTX overexpression mitigated ferroptosis of MGF-induced neurons through the miR-142-5p/GABPB1 axis. In conclusion, lncRNA FTX inhibited ferroptosis of MGF-induced rat hippocampal neurons via the miR-142-5p/GABPB1 axis.
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Current data suggest a hypothesis of vascular pathogenesis for the development and progression of Alzheimer's disease (AD). To investigate this, we studied the association of apolipoprotein E4 (APOE4) gene on microvessels in human autopsy-confirmed AD with and without APOE4, compared with age/sex-matched control (AC) hippocampal CA1 stratum radiatum. AD arterioles (without APOE4 gene) had mild oxidative stress and loss of vascular endothelial growth factor (VEGF) and endothelial cell density, reflecting aging progression. ⋯ This cell over-proliferation was inhibited with the antioxidants N-acetyl cysteine and MnTMPyP, the HIF-1α inhibitor echinomycin, the VEGFR-2 receptor blocker SU1498, the protein kinase C (PKC) ε knock-down (KD) and the extracellular signal-regulated kinase 1/2 (ERK) inhibitor FR180204. The PKCε KD and echinomycin decreased VEGF and/or ERK. In conclusion, AD capillaries and arterioles in hippocampal CA1 stratum radiatum of non-APOE4 carriers are related with aging, while those in APOE4 carriers with AD are related with pathogenesis of cerebrovascular disease.
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Case Reports
Functional Evaluation of a Novel GRIN2B Missense Variant Associated with Epilepsy and Intellectual Disability.
Epilepsy, a neurological condition, is widely prevalent among individuals with intellectual disability (ID). It is well established that N-methyl-D-aspartate (NMDA) receptors play an important role in both epilepsy and ID. Autosomal dominant mutations in the GRIN2B gene, which encodes the GluN2B subunit of the NMDA receptor, have been reported to be associated with epilepsy and ID. ⋯ It is accompanied by reduced delivery of the receptors to the cell membrane and a decrease in glutamate affinity. Moreover, primary neurons expressing GluN2B-K1091T also exhibited impaired surface expression of NMDA receptors, a reduction in dendritic spine number and excitatory synaptic transmission. In summary, our study reports a novel GRIN2B mutation and provides functional characteristics of this mutation in vitro, thereby contributing to the understanding of GRIN2B variants in epilepsy and ID.
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Alzheimer's disease (AD) is the most common neurodegenerative disease, and currently, no effective treatment strategies exist for this condition. MicroRNAs (miRNAs) have emerged as promising therapeutic targets of AD. Previous studies have highlighted the significant role of miR-146a-5p in regulating adult hippocampal neurogenesis (AHN). ⋯ Interestingly, both miR-146a-5p antagomir and p-Stat3 inhibitor obviously rescued neurogenesis and pattern separation in APP/PS1 mice. Moreover, application of miR-146a-5p agomir reversed the protective effects of Klf4 upregulation. These findings open new avenues for protection against AD through the modulation of neurogenesis and cognitive decline via the miR-146a-5p/Klf4/p-Stat3 pathway.