摘要
背景:阿尔茨海默病(AD)的早期阶段是在与学习和记忆相关的脑区内微调神经元电路的中断。这种调整是从调节皮层网络功能的兴奋性和抑制性输入的微妙的平衡中获得的。这种稳态可塑性大脑中相应的信息传递的动态提供了依据。兴奋性突触传递的主要是由谷氨酸能突触而抑制突触传递涉及GABA能和甘氨酸信号驱动。 GABA能细胞,负责在成人大脑抑制传输,最近已成为AD研究的重点。GABA能中间神经元是β淀粉样蛋白的靶点,这一发现表明兴奋性/抑制平衡的异常有助于皮质调节的变化,可能与病理发展有关。因此,了解有关GABA能改变分子的细节可以更好的帮助我们了解AD的发病机制。 目的:本文回顾了最近的研究,这些研究说明了早期改变的概念,AD的抑制电路和考虑其对膜GABA成分功能,细胞和微电路的水平的影响。 结论:基于AD的GABA能细胞和对微电路的特殊兴趣,这些方法可能会导致新的假设,动物模型和治疗策略。
关键词: β-淀粉样蛋白,GABA能中间神经元,远程投射神经元,神经回路,突触传递
Current Alzheimer Research
Title:GABAergic Microcircuits in Alzheimer's Disease Models
Volume: 14 Issue: 1
Author(s): Vincent Villette and Patrick Dutar
Affiliation:
关键词: β-淀粉样蛋白,GABA能中间神经元,远程投射神经元,神经回路,突触传递
摘要: Background: The early phase of Alzheimer's disease (AD) involves the disruption of finely tuned neuronal circuitry in brain regions associated with learning and memory. This tuning is obtained from the delicate balance of excitatory and inhibitory inputs which regulate cortical network function. This homeostatic plasticity provides a dynamic basis for appropriate information transfer in the brain. Excitatory synaptic transmission is driven mainly by glutamatergic synapses whereas inhibitory synaptic transmission involves GABAergic and glycinergic signaling.
GABAergic cells, responsible for inhibitory transmission in adult brain, have recently become the subject of study in AD research. The discovery that GABAergic interneurons are targets of the amyloid-beta (Aβ) peptide suggest that deregulation of the excitatory/inhibitory balance contributes to changes in cortical regulation, possibly with consequences for the development of the pathology. Thus, understanding the molecular details involved in GABAergic alterations may provide insight into the pathogenesis of AD. Objective: Here, we review recent discoveries illustrating the concept of early alterations to the inhibitory circuits in AD and consider their functional implications for GABAergic components at membrane, cellular and microcircuit levels. Conclusion: We look at approaches that may lead to new hypotheses, animal models and therapeutic strategies based on GABAergic cells in AD with particular interest in microcircuits.Export Options
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Cite this article as:
Vincent Villette and Patrick Dutar , GABAergic Microcircuits in Alzheimer's Disease Models, Current Alzheimer Research 2017; 14 (1) . https://dx.doi.org/10.2174/1567205013666160819125757
DOI https://dx.doi.org/10.2174/1567205013666160819125757 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
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