博尔纳病毒改变大鼠海马H4K5乙酰化所致学习记忆障碍的机制研究

项目名称： 博尔纳病毒改变大鼠海马H4K5乙酰化所致学习记忆障碍的机制研究

项目编号： No.81500921

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 刘霞

作者单位： 司法鉴定科学研究院

项目金额： 17.5万元

中文摘要： 博尔纳病毒（BDV）感染和人类精神疾病密切相关，引起认知障碍。虽然对BDV的发病机制进行了大量的探讨，但其确切机制仍不清晰，尤其在染色体可塑性及组蛋白修饰导致发病的层面仍是一个盲区。课题组前期研究发现BDV感染引起H4K5等多个组蛋白赖氨酸位点乙酰化修饰改变及部分乙酰转移酶（HATs）和去乙酰化酶（HDACs）改变。本研究以BDV感染的SD大鼠海马神经元和BDV感染新生SD大鼠为研究对象，在细胞水平探讨BDV调控HATs/HDACs的可能机制，探讨BDV是否通过干扰 H4K5乙酰化（H4K5ac）影响神经元突触可塑性；在整体动物水平探讨H4K5ac改变是否通过影响神经元突触可塑性及学习记忆相关基因表达引起感染动物的学习记忆障碍。本研究拟在组蛋白修饰调控基因表达层面寻找BDV感染引起神经元突触可塑性改变和认知功能障碍的重要发病机制，为BDV感染防治提供新策略。

中文关键词： 博尔纳病毒；组蛋白乙酰化；基因表达；突触可塑性；学习记忆障碍

英文摘要： Borna disease virus (BDV) infection is closely related to human mental illness, induces cognitive impairment. Notwithstanding abundant discussion of BDV -driven pathophysiology, it remains elusive to illuminate mechanism of BDV infection from the perspective of chromosome plasticity and histone modification. Our early study found BDV infection interferes with the acetylation on H4K5 and several other histone lysine sites, and disturbs some HATs and HDACs. This study focuses on BDV-infected rat hippocampal neurons and newborn SD rats, explores the possible mechanism of BDV regulating HATs/HDACs and whether BDV disturbs neuronal synaptic plasticity by interfering with H4K5 acetylation (H4K5ac) in vitro; explores whether expression change of H4K5ac induces learning and memory impairment in BDV-infected animals by interfering with neuronal synaptic plasticity-related and learning and memory-related gene expression. The present study aims at finding important mechanism of BDV infection disturbing neuronal synaptic plasticity and inducing cognitive dysfunction from the perspective of histone modification regulating gene expression, and providing the the novel strategy for the prevention and treatment of BDV infection.

英文关键词： Boran disease virus ;histone acetylation;gene expression;synaptic plasticity;learning and memory impairment