Role of GABAA receptors in EEG activity and spatial recognition memory in aged APP and PS1 double transgenic mice
Role of GABAA receptors in EEG activity and spatial recognition memory in aged APP and PS1 double transgenic mice
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GABAA受体对老年APP和PS1双转基因小鼠脑电活动和空间识别记忆的作用
DOI：
10.1016/j.neuint.2019.104542
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发表时间：
2019-12-01
影响因子：
4.2
通讯作者：
Wang, Jianhong
中科院分区：
文献类型：
--
作者：
Fu, Yu;Li, Liane;Wang, Jianhong
阿尔茨海默病（AD）是痴呆的主要原因，目前没有有效的治疗方法。然而，靶向衰老机制可能会改善结果，γ-氨基丁酸（GABA）系统的改变可能对老年认知能力下降的治疗有影响。我们研究了GABA系统对老年APP和PS1转基因小鼠脑活动的影响。低剂量（0.1 mg/kg i. p.）GABA（A）激动剂蝇蕈醇和拮抗剂荷包牡丹碱分别用于中度系统激活和抑制。在自发状态下和Y-迷宫中记录海马（Hip）和前额叶皮层（PFC）的EEG。基本上，AD小鼠表现出增加的自发EEG δ（2-4 Hz）和减少的自发EEG α（8-12 Hz）活动在髋关节中，和减少的Y-迷宫EEG θ（4-8 Hz）活动在PFC中。有趣的是，GABA（A）的激活和抑制在AD小鼠中减少EEG δ活动和增加的EEG θ活动在PFC中，和在Y-迷宫测试期间行为上改善空间识别记忆。在PFC中也观察到自发EEG δ活动减少。具体而言，GABA（A）激活主要影响PFC中的低频EEG（2-12 Hz）活动，而抑制则影响PFC和Hip中许多频率的EEG活动。这些数据为AD小鼠大脑活动较慢提供了证据。重要的是，GABA（A）激活和抑制后空间记忆的改善可以通过某些区域的脑节律恢复来解释。我们的研究强调了GABA（A）药物在改善AD认知障碍和恢复神经网络活动方面的潜在临床用途。
Alzheimer's disease (AD) is a leading cause of dementia, with no effective treatment currently available. However, targeting the aging mechanism may improve outcomes and gamma-aminobutyric acid (GABA) system alteration could have implications for treatment of cognitive decline in old age. We studied the effects of the GABA system on brain activity in aged APP and PS1 transgenic mice. Low dose (0.1 mg/kg i.p.) GABA(A) agonist muscimol and antagonist bicuculline were administered for moderate system activation and inhibition, respectively. EEGs from the hippocampus (Hip) and prefrontal cortex (PFC) were recorded under spontaneous state and during Y-maze performance. Basally, AD mice exhibited increased spontaneous EEG delta (2-4 Hz) and decreased spontaneous EEG alpha (8-12 Hz) activity in the Hip, and decreased Y-maze EEG theta (4-8 Hz) activity in the PFC. Interestingly, GABA(A) activation and inhibition in AD mice reduced EEG delta activity and increased EEG theta activity in the PFC, and behaviorally improved spatial recognition memory during Y-maze testing. Decreased spontaneous EEG delta activity was also observed in the PFC. Specifically, GABA(A) activation primarily affected low frequency EEG (2-12 Hz) activity in the PFC, whereas inhibition affected EEG activity across many frequencies in the PFC and Hip. These data provide evidence for slower brain activity in AD mice. Importantly, improved spatial memory after GABA(A) activation and inhibition may be explained by brain rhythm recovery in certain regions. Our study highlights the potential clinical use of GABA(A) drugs to improve cognitive disorders and restore neural network activity in AD.