I组代谢性谷氨酸受体介导的CREB信号通路在迷路损伤后前庭记忆中的调控作用研究

研究证实学习记忆功能参与了机体损伤后的神经重塑，且核蛋白cAMP反应元件结合蛋白（CERB）通路是记忆形成的关键环节。我们前期发现：单侧迷路切除（UL）后前庭神经内侧核（MVN）和小脑绒球内代谢性谷氨酸受体（mGluRs）和脑源性神经生长因子（BNDF）随前庭代偿过程而动态变化，而I组mGluRs和BNDF是CREB信号通路的重要环节。据此我们提出：mGluRs介导的前庭记忆机制可能参与了UL后前庭代偿，且与代偿程度相关。本项目研究大鼠UL后，不同神经核团（MVN、小脑绒球）内I组mGluRs、CREB激活和抑制通路相关信号分子及其下游产物的动态表达变化和水平，并通过研究I组mGluRs拮抗剂、CREB通路相关分子反义寡核苷酸对前庭代偿中CREB通路的影响，探讨分析“I组mGluRs-CREB信号通路”对迷路损伤后前庭记忆的调控作用，初步阐明记忆功能与前庭代偿的关系及可能的分子机制。

It is verified that the mechanism of study and memory were participated in the neural plasticity after damage, and the cAMP response element-binding protein (CREB) is a key signal pathway for development of memory. Our previous studies demonstrated that the metabotropic glutamate receptors (mGluRs) and brain-derived neurotrophic factor (BDNF) showed a dynamic change in the medial vestibular nucleus (MVN) and flocculus after unilateral labyrinthectomy (UL) in rat. Furthermore, both Group I mGluRs (mGluR1 and mGluR5) and BNDF are important factors in CREB signal pathway. Based on these findings, we proposed that vestibular memory induced by the group I mGluRs take part in the development of vestibular compensation after UL in rat. In the study, we investigated that dynamic change of Group I mGluRs and signal factors related to the CREB (CREB, eIF2α, c-Fos and BDNF mRNA) in MVN and flocculus in the different stage after UL. The regulatory mechanism of mGluRs on the CREB signal pathway was also studied by group I mGluRs antagonist and CREB antisense oligodeoxynucleotide. The objective of this study is to investigate the memory mechanism induced by group I mGluRs in the MVN and flocculus after UL, which based a theoretical foundation for vestibular rehabilitation treatment and prevention vestibular decompensation in clinical.