蛋白激酶A介导的大脑神经递质“半球偏侧化”改变在母体慢性应激所致子代行为异常的作用机制研究

项目名称： 蛋白激酶A介导的大脑神经递质“半球偏侧化”改变在母体慢性应激所致子代行为异常的作用机制研究

项目编号： No.31300927

项目类型： 青年科学基金项目

立项/批准年度： 2014

项目学科： 医药、卫生

项目作者： 黄月君

作者单位： 汕头大学

项目金额： 25万元

中文摘要： 本项目在前期研究中发现，母鼠慢性应激会导致子鼠在强迫游泳试验中的"应激应对能力"和在水迷宫试验中的"学习记忆能力"下降，并能检测到子鼠大脑的蛋白激酶A信号通路、前额叶皮质的多巴胺系统和海马的5-羟色胺系统出现异常，且这些改变主要发生在右侧大脑半球，存在"半球偏侧化"改变。因此，我们提出假设：母体慢性应激所致子代行为异常的机制可能与蛋白激酶A信号介导的大脑神经递质"半球偏侧化"改变有关。为论证该假设，本项目将在慢性不可预见性应激母鼠模型上，采用微型高场磁共振成像系统及磁共振波谱分析，并运用神经行为学试验、分子生物学技术，明确母体慢性应激对子代行为异常发生的影响，探寻慢性应激子代大脑蛋白激酶A介导的神经递质代谢以及神经蛋白分布和含量的"半球偏侧化"改变，并从遗传、环境、脑功能与行为之间相互作用的角度探讨母体慢性应激所致子代行为异常的发生机制。研究结果可拓展对儿童心理行为疾病的认识。

中文关键词： 应激；子代；海马；谷氨酸；蛋白激酶A

英文摘要： In our preliminary studies, we found the maternal chronic stress would lead to the decreased coping ability of offspring rats in the forced swimming test and decreased learning and memory ability of offspring rats in the water maze test. We also found the maternal stress would affect the protein kinase A signaling pathway in the brain, the dopamine system in the prefrontal cortex and the serotonin system in the hippocampus of offspring rats. The above findings occurred in the right hemisphere, which was the "hemispheric lateralization" change. Therefore, we hypothesized that the mechanism of abnormal behavior in the offspring which was due to the maternal chronic stress may be related to the protein kinase A signal-mediated "hemispheric lateralization" change in the brain. In order to demonstrate the assumptions, the project will use the chronic unpredictable stress maternal rat model, and apply miniature high-field magnetic resonance imaging, magnetic resonance spectroscopy, neural behavioral tests and molecular biology techniques to determine the influence of maternal chronic stress on the behavior of offspring, and investigate the protein kinase A signal-mediated "hemispheric lateralization" change in the metabolism of neurotransmitters and the distribution of neuronal protein. The project will explore the me

英文关键词： stress；offspring；hippocampus；glutamate；protein kinase A