在空間學習和記憶形成後對海馬迴中表觀遺傳修飾調控 miRNA 表現的研究研;The investigation of the epigenetic modification regulated mi-RNA induction in the hippocampus after spatial learning and memory formation

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题名:	在空間學習和記憶形成後對海馬迴中表觀遺傳修飾調控 miRNA 表現的研究研;The investigation of the epigenetic modification regulated mi-RNA induction in the hippocampus after spatial learning and memory formation
作者:	司峇塔;SIMANULLANG, BASTA
贡献者:	生命科學系
关键词:	表觀遺傳;mi-RNAs 誘導;甲基化;Epigenetic;mi-RNAs induction;Methylation
日期:	2019-08-01
上传时间:	2019-09-03 14:33:37 (UTC+8)
出版者:	國立中央大學
摘要:	行為是由環境刺激驅動的，這種刺激通過許多分子機制觸發大腦活動。學習和記憶的過程包括刺激誘導的海馬神經元之間的突觸連接的變化，其在長期的體細胞和情節記憶的形成中起關鍵作用。通過Morris 水迷宮實驗與RNA 的分析表明，在有學習和未學習的小鼠之間存在微小RNA 表達不同。屬於轉錄後調節因子的miR-466f-3p 在腦中大量表現且其在基因中位於一基因的內含子-10 中（Sfmbt2）。然而，宿主基因（sfmbt2）的mRNA 表現量與miR-466f-3p 顯著不同。表觀遺傳修飾，如DNA 甲基化可影響基因表達。5′Aza-dC，一個甲基轉移酶抑製劑，用於處理海馬迴原代培養神經元導致Bdnf，Nrf2 和Sfmbt2 mRNA 與miR466f-3p 的表現量增加。根據實驗結果顯示，miR-466f 家族的啟動子區域中其甲基化模式在有學習和未學習的小鼠之間沒有顯著差異。證據表明，在Morris 水迷宮的應激下，DNA 甲基化的變化不直接參與誘導miR-466f-3p 在海馬依賴性空間學習和記憶形成的調節。;Behavior is driven by environmental stimulation that triggers brain activity with lots of molecular mechanisms. The process of learning and memory contains stimulation-induced changes that happen in the synaptic connections between neurons in the hippocampus, which plays a pivotal role in the formation of long term somatic and episodic memories. By Morris water maze experiment and RNA analysis, we show that some micro-RNAs (miRNA) are expressed differently between learned and unlearned mice. One of the miRNAs, miR-466f-3p, which belongs to post transcriptional regulator, is abundantly express in brain and generated in the intron-10 of Sfmbt2 gene. However, the mRNA expression of Sfmbt2 is significantly different from miR-466f-3p. Inhibition of epigenetic modification, such as DNA methylation, can affect gene expression. Treatment of 5’Aza-dC, a methyltransferase inhibitor, to the hippocampal primary culture neuron causes Bdnf, Nrf2, Sfmbt2 mRNA and miR466f-3p expression increased. However, the methylation pattern in the promoter region of the miR-466f cluster is not significantly different between learned and unlearned mice. The evidence show that the changes of DNA methylation under the stress of the Morris water maze indirectly participate in the regulating of miR-466f-3p induction in the hippocampus-dependent spatial learning and memory formation. Keywords: Epigenetic, mi-RNAs induction, Methylation
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