| Summary: | 碩士 === 國立成功大學 === 生理學研究所 === 103 === MicroRNAs (miRNAs) have attracted much attention at neuronal development, synapse formation and synaptic plasticity regulation. Besides, emerging evidences suggest that miRNAs are involved in the neuroprotective effects in many neurological disorders, such as brain ischemia, excitotoxicity and Alzheimer's disease. One previous study published from our laboratory indicated that miR-196a ameliorates phenotypes of Huntington’s disease in cells, transgenic mice and patient-derived induced pluripotent stem cell models, indicating that miR-196a may play an important role in neuroprotection. Recently, studies have revealed that miR-196a could directly interact with nuclear factor-keppa B inhibitor alpha (IĸBα) 3'UTR to suppress IκBα expression and subsequently promotes nuclear factor kappa B (NF-κB) activation. Therefore, we hypothesize miR-196a might have neuroprotective effects through NF-ĸB activation. Here, we focuse on the effects of miR-196a on synaptic plasticity and anti-apoptotic functions. Our results suggest that IĸBα is down-regulated and NF-ĸB is activated as miR-196a was overexpressed in cells and transgenic mouse models. Additionally, the brains of miR-196a transgenic mice display higher expression of calbindinD-28k, related to synaptic plasticity. Furthermore, the miR-196a transgenic mice express higher vesicle-associated membrane protein 1 and c-fos, markers for synaptic proteins and neuron activities respectively, compared to those of wild type mice. Besides, miR-196a down-regulates the expression of pro-apoptotic protein Bim and elevates cell viability in the presence of oxidative stress in vitro. Our results identify a possible function of miR-196a on neuroprotection through NF-ĸB activation, and may provide a potential therapeutic strategy for several neurodegenerative diseases.
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