基底前脑-丘脑网状核GABA能神经元介导摩脊法调控非快速眼动睡眠机制研究

Non-rapid eye movement (NREM) sleep restores the brain cognitive skills through regulating brain energy metabolism and synaptic balance. Abnormality of NREM sleep is closely related to hot issues in medicine. Drugs improve NREM sleep but suppress REM sleep, curative effect mechanism of back Tuina is not known which can effectively regulate NREM sleep. We intend to certain that NREM sleep of insomnia model rat is regulated by Moji manipulation. We will use fMRI technology to observe activation and function connection of NREM regulation brain district after Moji manipulation.And we will combine Cortical Brain Electrophysiology, Optogenetics techniques and Immunohistochemical technique to study whether GABA-ergic neurons mediates curative effect of NREM sleep regulated by Moji manipulation.These will verify the hypothesis that Moji manipulation stimulates GABA-ergic neurons in the basal forebrain and thalamus reticular nucleus, and inhibits arousal neurons or cerebral cortex neurons in the brain to regulate the NREN sleep. This project will provide reliable empirical evidence for Moji manipulation treating NREM-related diseases, and have a positive impact on the innovative development of tuina.

非快速眼动（NREM）睡眠调节脑能量代谢和神经突触平衡以恢复大脑认知能力；NREM睡眠异常与医学热点问题密切相关。药物改善NREM睡眠却抑制快速眼动睡眠，背部推拿可有效调控NREM睡眠但其作用机制未明。本项目拟明确摩脊法干预失眠模型大鼠调控NREM睡眠效应；采用fMRI技术观察摩脊法对NREM调控脑区激活及功能连接的影响；以皮层脑电作为效应指标，观察光遗传技术激活/失活基底前脑及丘脑网状核神经元前后，摩脊法调控NREM效应变化，结合免疫组化技术确定光刺激激活/失活神经元类型，探索GABA能神经元在摩脊法调控NREM睡眠效应中的介导作用。综合上述验证假说：摩脊法刺激上传至脑内调控NREM睡眠神经网络，激活或增强基底前脑与丘脑网状核GABA能神经元功能，抑制脑内促醒神经元或大脑皮层，调控NREN睡眠。本项目将为摩脊法治疗失眠等NREM相关疾病提供可靠的实验证据，将对推拿学创新发展产生积极影响。

NREM睡眠通过调节脑能量代谢及神经突触稳态以保证大脑良好认知表现，NREM睡眠异常与注意力缺陷多动障碍、生长发育不良、阿尔茨海默病、衰老等医学热点密切相关；背部推拿可有效调控NREM睡眠但其作用机制未明。为明确摩脊法调控NREM睡眠效应及机制，本项目在摩脊法干预NREM睡眠减少模型大鼠效应平台上，采用fMRI技术分析摩脊法对NREM睡眠调控脑区功能连接的影响，观察光遗传沉默对摩脊法调控NREM睡眠效应的影响。初步明确了脑内GABA能神经元在摩脊法调控NREM睡眠效应中的介导作用：证实了摩脊法对NREM睡眠减少模型大鼠具有趋于正常的调节作用；发现摩脊法干预后丘脑与前边缘皮层、前扣带、杏仁核、伏隔核功能连接增强，伏隔核与上述脑区功能连接减弱；发现摩脊法对NREM睡眠减少模型大鼠的正性作用在光遗传学刺激失活TRN GABA能神经元后消失。提示摩脊法强化丘脑功能连接、弱化伏隔核功能连接，上调TRN GABA能神经元功能，实现其对NREM睡眠减少模型大鼠趋于正常的调节作用，而杏仁核与海马可能也参与了这一过程。