《生命科学》 2014, 26(1): 44-49

环路失稳-老年痴呆症癫痫样症状发生机制研究进展

周　斌，周煜东^*

(浙江大学医学部神经科学研究所，卫生部医学神经生物学重点实验室，浙江省神经生物学重点实验室，杭州 310058)

摘　要：摘　要：β- 淀粉样蛋白(amyloid-β， Aβ) 聚集是阿尔茨海默症(Alzheimer’s disease， AD) 的典型病理特征之一。虽然病理水平的Aβ 对兴奋性突触功能起抑制作用，但Aβ 对抑制性中间神经元的抑制作用使局部神经网络发生兴奋与抑制的不平衡，从而产生自发性癫痫样活动。AD 早期对兴奋性神经元的去抑制作用很可能是针对Aβ 引起的兴奋性突触功能降低的一个代偿机制。试从环路失衡的角度对AD 及其癫痫症状的发病机制进行综述，并讨论通过调节神经网络的兴奋性治疗AD 的新思路。

Circuit instability-progress in mechanisms underlying epileptiform activity in Alzheimer’s disease

ZHOU Bin， ZHOU Yu-Dong^*

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

Abstract: Abstract: Amyloid-β (Aβ) deposition is one of the key pathological characters of Alzheimer’s disease (AD). Although pathological levels of Aβ cause excitatory synapse depression， inhibitory effects of Aβ on GABAergic inhibitory neurons render excitation-inhibition imbalance in local neuronal networks， leading to epileptiform discharges. This disinhibition of excitatory neurons may be a compensatory mechanism in response to Aβ-induced excitatory synapse dysfunction. Here we review the pathogenesis of AD and AD-associated epilepsy from the view of circuit instability， and discuss regulating network activity as a new strategy in the treatment of AD.