GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer's disease.
GABAergic dysfunction, neural network hyperactivity and memory impairments in human aging and Alzheimer's disease.
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DOI：
10.1016/j.semcdb.2021.01.005
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发表时间：
2021-08
影响因子：
7.3
通讯作者：
Eich TS
中科院分区：
文献类型：
--
作者：
Jiménez-Balado J;Eich TS
在这篇综述中，我们关注γ-氨基丁酸能（GABA能）系统在人类年龄相关的情景记忆障碍中的潜在作用，特别关注阿尔茨海默病（AD）。成熟的动物模型已经表明，GABA在调节和同步海马中的神经元信号传导中起核心作用，海马是对情景记忆至关重要的脑区，其在AD过程中经历早期和显著的形态和功能变化。人类的神经影像学研究已经记录了海马体中的过度活跃和默认模式网络中静息状态功能连接的丧失，默认模式网络本身显著地包括AD风险个体中的海马体-预示情景记忆下降。载脂蛋白ε4是AD的最高遗传风险因子，与动物模型中的GABA能功能障碍和人类的情景记忆障碍相关。总之，这些发现表明，GABA可能是一个复杂的因素系统中的关键，最终导致AD的主要临床标志：情景记忆丧失。在这里，我们将回顾支持这一假设的文献的现状。首先，我们将集中在GABA能系统的分子和细胞基础及其在记忆和认知中的作用。接下来，我们在动物模型和人体研究中报告了AD和正常衰老中GABA失调的证据。最后，我们概述了GABA能功能障碍的模型的基础上，在人类的功能性神经影像学研究的结果，这表明海马活动过度，情节记忆任务的同时，甚至之前的AD诊断，沿着的因素，可能会调节这种关联。
In this review, we focus on the potential role of the γ-aminobutyric acidergic (GABAergic) system in age-related episodic memory impairments in humans, with a particular focus on Alzheimer’s disease (AD). Well-established animal models have shown that GABA plays a central role in regulating and synchronizing neuronal signaling in the hippocampus, a brain area critical for episodic memory that undergoes early and significant morphologic and functional changes in the course of AD. Neuroimaging research in humans has documented hyperactivity in the hippocampus and losses of resting state functional connectivity in the Default Mode Network, a network that itself prominently includes the hippocampus—presaging episodic memory decline in individuals at-risk for AD. Apolipoprotein ε4, the highest genetic risk factor for AD, is associated with GABAergic dysfunction in animal models, and episodic memory impairments in humans. In combination, these findings suggest that GABA may be the linchpin in a complex system of factors that eventually leads to the principal clinical hallmark of AD: episodic memory loss. Here, we will review the current state of literature supporting this hypothesis. First, we will focus on the molecular and cellular basis of the GABAergic system and its role in memory and cognition. Next, we report the evidence of GABA dysregulations in AD and normal aging, both in animal models and human studies. Finally, we outline a model of GABAergic dysfunction based on the results of functional neuroimaging studies in humans, which have shown hippocampal hyperactivity to episodic memory tasks concurrent with and even preceding AD diagnosis, along with factors that may modulate this association.
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影响因子：
168.9
作者：
Ballard, Clive;Gauthier, Serge;Jones, Emma
通讯作者：
Jones, Emma
影响因子：
14.5
作者：
Bar-Klein, Guy;Lublinsky, Svetlana;Friedman, Alon
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3.3
作者：
Beas BS;McQuail JA;Ban Uelos C;Setlow B;Bizon JL
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影响因子：
16.2
作者：
Bakker A;Krauss GL;Albert MS;Speck CL;Jones LR;Stark CE;Yassa MA;Bassett SS;Shelton AL;Gallagher M
通讯作者：
Gallagher M
影响因子：
4.2
作者：
Bakker, Arnold;Albert, Marilyn S.;Krauss, Gregory;Speck, Caroline L.;Gallagher, Michela
通讯作者：
Gallagher, Michela