CeA-Vmo通路中CRH能神经元参与调控心理应激致口颌肌紧张度升高的机制研究

Psychological stress plays an important role in the occurrence and development of jaw muscle dysfunction. Our team has explored the negative effects of psychological stress on the stomatognathic system as well as the concerned peripheral mechanism. However, it is still unclear how psychological stress results in jaw muscle overactivity via the central neural system. Also, the underlying regulatory mechanism needs to be confirmed. In the central neural system, trigeminal motor nucleus (Vmo) innervates jaw muscle movement, while the central amygdaloid nucleus (CeA) is responsible for emotional stress. There are close neural fiber links between them. We previously indicated that CeA and Vmo neurons could be activated by psychological stress. Additionally, it has been demonstrated that corticotropin releasing hormone (CRH) neurons in CeA are obviously activated in the condition of psychological stress. Therefore, we speculate that the CeA-Vmo neural pathway and the CRH neurons in this neural pathway may involve in the jaw muscle overactivity induced by psychological stress. For verifying the hypothesis, we intend to take the advanced nerve center as the breakthrough point for revealing the CeA-Vmo related central neural regulatory mechanism underlying the psychological stress induced jaw muscle overactivity with animal behavioral tests, neural tracing, optogenetics and electrophysiology, etc. The whole project is expected to explore the intact mechanism chain of psychological stress - central neural system - peripheral nervous system - jaw muscle dysfunction.

心理应激在口颌肌功能紊乱的发生发展中起到重要作用，本课题组已对心理应激的口颌系统负性效应、外周机制等进行了深入研究。然而，对于心理应激究竟是如何引发口颌肌紧张这一负性效应的高级中枢调控机制目前尚不清楚。在中枢神经系统，支配口颌肌运动的三叉神经运动核（Vmo）与发生情绪应激的关键核团中央杏仁核（CeA）存在密切的神经纤维联系，形成解剖学通路。本课题组前期研究发现，心理应激后CeA与Vmo神经元被激活，加之文献报道心理应激可使CeA中促肾上腺皮质激素释放激素（CRH）能神经元激活，提示我们CeA-Vmo通路以及CRH能神经元很可能在心理应激致口颌肌紧张的过程中扮演了重要角色。本项目拟以高级神经中枢为切入点，运用动物行为学、神经束路追踪、光遗传学、电生理学等技术，深入研究心理应激致口颌肌紧张度升高的CeA-Vmo相关高级中枢调控机制，以期探明完整的心理应激-中枢-外周-口颌肌功能紊乱发生机制链。

现代社会中，心理应激与人类主要疾病密切相关，心理应激在口颌肌功能紊乱的发生发展中起到重要作用，前期本课题组已对心理应激的口颌系统负性效应、外周机制等进行了深入研究。在明确心理应激对口颌肌运动功能的负性效应以及外周调控机制研究基础上，本课题选择高级神经中枢作为切入点与关注点，本课题拟在建立急/慢性动物心理应激模型的基础上，采用行为学、形态学、分子生物学等方法进一步有针对性地对心理应激状态致口颌肌紧张的高级中枢调控机制进行深入探索，本项目发现心理应激可导致口颌肌形态功能的改变，而口颌肌功能亢进使其向三叉神经核团的兴奋性投射增加，神经元兴奋性增强。心理应激后，三叉神经核、海马以及杏仁核核团内神经活化，相关分子的表达出现变化，使得我们进一步明确了心因性口颌肌疾病的相关中枢神经系统调控机制，初步揭示了心理应激-中枢-外周-口颌肌功能紊乱发生机制链，为全面、系统地认识口颌肌功能紊乱的心理病因学发病机制奠定了基础，并为心因性口颌肌功能紊乱的防治提供了坚实的实验依据。