成体齿状回神经干细胞microRNA-132/212在阿片成瘾中的作用及分子机制

项目名称： 成体齿状回神经干细胞microRNA-132/212在阿片成瘾中的作用及分子机制

项目编号： No.81471353

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 崔彩莲

作者单位： 北京大学

项目金额： 70万元

中文摘要： 研究表明，成体海马齿状回神经元新生可参与记忆痕迹的清除。非编码核酸microRNA-132/212家族可直接抑制其它基因的mRNA翻译，参与调控齿状回神经干细胞发育。然而，成体齿状回神经干细胞内的microRNA-132/212，如何调控海马齿状回神经元新生及成瘾记忆，仍不清楚。本课题计划：①观测阿片自给药大鼠齿状回神经干细胞发育，胞内CREB通路、microRNA-132/212及靶基因水平变化；②构建稳定高表达μ-阿片受体的N2a细胞系，确定吗啡处理后N2a细胞发育变化，是否受胞内CREB诱导的microRNA-132/212水平及其主要靶基因影响；③在体验证，时空特异性地过表达microRNA-132及其靶基因对大鼠阿片自身给药形成、消退/清除和重建的影响。以期证明CREB诱导性的microRNA-132/212家族及其靶基因通过调控成体海马齿状回神经元新生，参与药物成瘾记忆。

中文关键词： 吗啡；自身给药；microRNA-132/212；成体海马神经元新生；成瘾记忆

英文摘要： Previous studies indicate that adult hippocampal neurogenesis contributes to memory trace clearance. Non-coding nucleic acid microRNA-132/212 family can regulate the neural stem cell development through silencing other genes by inhibiting their mRNA translation. However, it still remains unclear how microRNA-132/212 within adult dentate gyrus neural stem cells control neurogenesis and addiction memory. In the present work,we plan to: ? observe the changes in dentate gyrus neurogenesis as well as the expression level of CREB signaling members, microRNA-132/212 and their putative target genes in the sub-population of neural stem cell-derived cells, based on morphine self-administration by rats; ? using the μ-opioid receptor over-expressing stable cell line (Neuro2a MOR), investigate whether the neural stem cell developmental outcome after morphine exposure is mediated by the CREB-induced microRNA-132/212 and their target molecules; ? verify that the over-expression of microRNA-132 and its novel target in a time-specific and cell type-restricted manner can affect the acquisition, extinction/clearance and reinstatement of morphine self-administration in rats. We aim to demonstrate that addiction memory can be controlled by CREB-induced microRNA-132/212 and their target molecules through the regulation of adult hippocampal neurogenesis.

英文关键词： Morphine;Self administration;microRNA-132/212;Adult hippocampal neurogenesis;Addiction memory