越来越多的研究证实咬合支持丧失作为危险因素对认知功能损害的影响，但机制尚不明确。血管性危险因素是认知损害和痴呆进程中非常重要的因素之一，其中一氧化氮(NO)信号通路在其致病中起重要的作用。咀嚼运动也会影响脑部血流，同时，本课题组前期研究发现咬合支持丧失影响脑内NO及其合酶的表达，推测NO信号通路在咬合支持丧失造成的认知损害中起着重要的作用。本课题拟建立慢性脑缺血咬合支持丧失动物模型，通过建模后不同时间点的认知行为学测试、脑血流监测、NO及其合酶表达与功能检测、NO相关下游基因筛查等方法，以及老年人群伴有慢性脑缺血的认知功能损害与咬合支持相关性的观察，研究咬合支持丧失对伴有慢性脑缺血的认知功能损害发生发展的影响和NO信号通路在其中的作用及分子调控机制，探究咬合支持丧失对脑认知功能损害的神经生理学机制，为揭示咬合影响脑功能的生物学机制提供理论依据，以期改善老年人的生活质量。

More and more studies confirm occlusal support loss as a risk factor for cognitive impairment in the aging population, but the mechanism is not very clear. Vascular risk factor is one of the very important factors in the process of cognitive impairment and dementia, wherein the nitric oxide signaling pathway plays an important role in its pathogenic process. The chewing movement can also affect blood flow in the brain. Our previous studies found that the loss of occlusal support affect the expression of nitric oxide and its synthase in brain, suggesting that the nitric oxide signaling pathway might play an important role in cognitive impairment caused by occlusal support loss. This project is intend to investigate the effect of occlusal support loss for development of cognitive dysfunction with chronic cerebral ischemia, the function and molecular mechanism of NO signaling pathway in this process by establishing the animal model of chronic cerebral ischemia and occlusal support loss, cognitive behavior, examining the cerebral blood flow, the expression and function of nitric oxide and its synthase, screening down-stream target gene by microarray annalysis, surveying the relationship of cognitive impairment with chronic cerebral ischemia and occlusal support loss in the old population. Through this study, we will discover neurophysiological mechanisms of cognitive impairment and occlusal support loss, reveal the biological mechanisms of effect of chewing movement on the function of brain, and provide the useful information for improving the life quality in old people.