CLOCK基因多态性与睡眠节律扰乱后感觉门控功能受损的关系研究

Researches showed: disruption of sleep rhythm can cause obvious impairment on people’s cognitive function, who work under extreme environments. Their sensory gating (SG) function could be impaired, and expression of circadian genes would change, including CLOCK gene, but the mechanism is still unclear. Animal researches showed that sensory gating function of mice with mutation of CLOCK gene was worse than wild mice, and behaved like patients of bipolar disorder. Polymorphism in the CLOCK gene was linked with more frequent episodes of mood disturbances and reduced need for sleep. These researches suggest that SG impairment caused by sleep disruption can be improved by adjusting expression of CLOCK gene. And we found that degree of cognitive impairment caused by disruption of sleep rhythm differentiated greatly between different people.We conclude: polymorphism in CLOCK gene is correlated with degree of impairment of sensory gating function after disruption of sleep rhythm. In this study, we will compare the expression changes and sensory gating function changes between different CLOCK genotype, in conditions of disruption of sleep rhythm and behavioral intervene. And we hope to clarify the mechanism of cognition impairment at molecular and neural function level, and provide theoretical basis for personal selection and intervene under extreme environment.

研究表明：睡眠节律扰乱影响极端环境从业人员认知功能，损害感觉门控功能（SG），并引起CLOCK基因表达的改变，但具体机制不明。动物实验显示CLOCK基因突变小鼠感觉门控功能下降，伴双向情感障碍类似行为异常。躁郁症患者CLOCK基因多态性与其情绪变化的频率增加及睡眠减少有关。提示调节CLOCK可能改善睡眠节律扰乱所致的门控功能受损，改善认知功能。我们前期发现睡眠节律扰乱所致的认知损害具有个体差异性。据此推测：CLOCK基因多态性与个体睡眠节律扰乱后感觉门控功能损害程度有关。本项目拟分析不同CLOCK基因表型个体在睡眠节律扰乱后，基因表达量变化及感觉门控功能变化的差异；在行为干预后，基因表达量变化及感觉门控功能变化的差异。在分子及认知神经功能水平深入研究不同基因表型引起不同认知功能损害的机制，为极端环境从业人员的选拔及干预提供依据。

已有研究表明，CLOCK基因多态性与个体应对睡眠节律扰乱导致的认知功能损害有关。本研究分析了中国人群CLOCK基因多态性的发生率，及不同CLOCK基因型的个体在睡眠节律扰乱后基本认知功能——感觉门控功能变化的差异，并探讨了心理弹性对这种认知功能损害的保护作用。本研究完成了中国被试CLOCK（rs53576）基因多态性流行病学调查，发现未突变比率为47.3%，含突变基因的个体比率为52.7%，远高于其他国家突变率；建立了实验室条件下睡眠节律扰乱模型；发现36小时完全睡眠剥夺会导致被试感觉门控功能显著受损；睡眠节律扰乱对于个体P50的波幅会产生显著影响，但对潜伏期影响不显著，表明睡眠节律扰乱会降低个体的感觉门控功能。不同基因型个体对比分析发现，CLOCK（rs53576）纯合子个体，相对于含突变的个体来说，受睡眠节律扰乱影响较小，但差异不显著，可能由于被试量相对较小的原因，后续增加被试后会进一步分析此效应。本研究第一次得到了CLOCK基因（rs53576）中国人群突变率，并且分析了这种突变对于睡眠节律扰乱导致的认知损害的影响，对于我国特种岗位人员选拔及心理干预具有重要的参考意义。