《生命科学》 2014, 26(1): 35-43

老年痴呆症的突触和神经环路机制

刘运进^1，2#， 潘洪玉^1，2#，孙秉贵^1，2*

(1 浙江大学医学院神经科学研究所，杭州 310058；2 卫生部医学神经生物学重点实验室，杭州 310058)

摘　要：摘　要：老年痴呆症的主要临床表现为认知功能严重受损，其原因可能是皮层与海马内的突触结构或功能障碍及神经环路活动异常所致。可溶性Aβ 尤其是Aβ 寡聚体( 而不是沉积在脑组织中的淀粉样斑块) 可能首先选择性地攻击GABA 能抑制性神经元，使海马或皮层内兴奋性神经元由于所受抑制减弱而过度兴奋，进而导致神经环路或网络活动异常。神经网络异常又通过一系列的代偿反应引起突触传递和突触可塑性受损。正常生理水平的tau 通过不同的机制在介导Aβ 的突触及神经环路毒性中扮演重要角色。

Synaptic and neural circuitry mechanisms of Alzheimer’s disease

LIU Yun-Jin^1，2#， PAN Hong-Yu^1，2#， SUN Bing-Gui^1，2*

(1 Institute of Neuroscience， Zhejiang University School of Medicine， Hangzhou 310058， China; 2 Key Laboratory of Medical Neurobiology of Ministry of Health of China， Hangzhou 310058， China)

Abstract: Abstract: Cognitive dysfunction is one of the major clinical features of Alzheimer’s disease (AD). Synaptic failure and aberrant network activity in the cortex and hippocampus may account for the cognitive impairment in AD. Soluble Aβ， especially Aβ oligomers， may attack the GABAergic interneurons selectively in the early stage of AD. Impairment of GABAergic interneurons results in hyperactivity of neurons and then aberrant circuitry/network activity in the hippocampus or cortex due to disinhibition. Neural circuity or network dysfunction may cause the impairment of synaptic transmission and plasticity through compensatory responses. Aβ-induced synaptic and circuity/network dysfunction is mediated by normal physiological levels of tau.