GABA神经元在Aβ诱导认知功能缺陷中的作用机制

The function and mechanism of GABA neurons in Aβ-induced cognitive deficits

阿尔茨海默病(Alzheimer’s disease,AD)是最常见的一种中枢神经系统退行性疾病,其主要特征是淀粉样斑块沉积、神经元大量丢失、神经原纤维缠结和认知功能缺陷。研究表明,β淀粉样蛋白(amyloidβ,Aβ)的聚集可能是AD发生过程中导致认知功能缺陷等病理变化的主要起始因子。然而,Aβ诱导病理变化的机制并不清楚。Aβ能够导致兴奋性神经元中谷氨酸能突触传递减少,从而使神经元网络活性受到抑制。但是,最近的研究表明,在AD模型中,Aβ能够引起神经元网络活性异常增加。γ-氨基丁酸能(γ-aminobutyric acid,GABA)抑制性中间神经元功能受损和活性降低可能是造成上述两种不同现象的原因。该文对GABA神经元在Aβ诱导的认知功能缺陷中作用及其机制,以及以GABA神经元为靶点治疗AD的研究现状进行综述。

Alzheimer＇s disease（AD） is the most common neurodegenerative disease characterized by amyloid plaques, neuronal loss, neurofibrillary tangles and cognitive deficits. Previous studies suggest that amyloid β（Aβ） abnormal deposition in the brain may be the major initial factor for neuropathology including cognitive deficits during AD. However, the mechanisms of Aβ-induced neuropathology are still unclear. Aβ causes the decrease of synaptic glutamatergic transmission which will induce the decrease of neural network activity. However, recent studies indicate that Aβ induces the aberrant neural network activity in AD model. Deficits and the decreased activity of γ-aminobutyric acid（GABAergic, GABA） inhibitory interneuron may be involved in this process. In the present paper, we will review the recent progress on the roles and the mechanisms of GABA neurons during Aβ-induced cognitive deficits, as well as on the treatment of AD through GABA interneurons.