海马CA1区5-HT1A受体调控偏侧咀嚼小鼠空间记忆的作用机制研究

偏侧咀嚼是常见的口腔不良习惯，对口腔功能和脑功能均产生重要影响，发病机制尚未阐明。本课题组首次发现偏侧咀嚼患者紧咬牙运动影响海马旁回激活的现象，而海马与学习记忆活动密切相关。海马CA1区5-HT1A受体及其下游CREB-BDNF通路与学习记忆关系尤为密切，但其参与偏侧咀嚼影响学习记忆的关系，迄今国内外尚无报道。在前期研究中我们发现偏侧咀嚼小鼠海马CA1区5-HT1A受体水平降低，推测5-HT1A受体可能通过调节CREB-BDNF相关信号通路，促进下游通路靶基因的转录，从而参与调控偏侧咀嚼小鼠空间记忆。为证实这一假说，本项目将采用细胞生物学、分子生物学和水迷宫行为学等实验方法，通过细胞实验和动物实验观察海马CA1区5-HT1A受体，CREB-BDNF通路上下游靶点，参与调控偏侧咀嚼小鼠空间记忆的作用机制，本课题将从新的视角阐明偏侧咀嚼运动中枢调控的分子机制，并为偏侧咀嚼的防治提供理论依据。

Chewing-side preference (CSP) is a commonly oral habits, which will lead to serious effects on stomatognathic system and brain function. However, the mechanism is not clear. Our research group for the first time found the phenomenon of parahippocampal activation in patients with CSP. Moreover, hippocampus is closely related with learning and memory. The 5-HT1A receptor in hippocampal CA1 region and its downstream CREB-BDNF pathway are particularly closely related to learning and memory. However, there are no reports on the relationship between the 5-HT1A receptors and learning and memory in patients with CSP. In previous studies, we found that the 5-HT1A decreased in mice with CSP, which is a new mechanism of 5-HT1A receptor regulating spatial memory in mice with CSP by regulating signal pathway of CREB-BDNF and promoting transcription of target genes in downstream pathway. To confirm this hypothesis, the project will observe the mechanism of 5-HT1A receptor in hippocampal CA1 region and the up-downstream target of CREB-BDNF pathway regulating spatial memory in mice with CSP by cytobiology, molecular biology and Water Maze experiments and a series of cell experiments and animal experiments. The research will elucidate the molecular mechanism of CSP from a new perspective, and provide theoretical basis for prevention and treatment of CSP.