年龄相关性认知衰退的分子机制：γ-氨基丁酸信号传导的作用
Molecular aspects of age-related cognitive decline: the role of GABA signaling.
作者信息
McQuail Joseph A, Frazier Charles J, Bizon Jennifer L
机构信息
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA.
Department of Neuroscience, University of Florida, Gainesville, FL 32610, USA; McKnight Brain Institute, University of Florida, Gainesville, FL 32610, USA; Department of Pharmacodynamics, University of Florida, Gainesville, FL 32610, USA.
出版信息
Trends Mol Med. 2015 Jul;21(7):450-60. doi: 10.1016/j.molmed.2015.05.002. Epub 2015 Jun 9.
Abstract
Alterations in inhibitory interneurons contribute to cognitive deficits associated with several psychiatric and neurological diseases. Phasic and tonic inhibition imparted by γ-aminobutyric acid (GABA) receptors regulates neural activity and helps to establish the appropriate network dynamics in cortical circuits that support normal cognition. This review highlights basic science demonstrating that inhibitory signaling is altered in aging, and discusses the impact of age-related shifts in inhibition on different forms of memory function, including hippocampus-dependent spatial reference memory and prefrontal cortex (PFC)-dependent working memory. The clinical appropriateness and tractability of select therapeutic candidates for cognitive aging that target receptors mediating inhibition are also discussed.
摘要
抑制性中间神经元的改变会导致与多种精神和神经疾病相关的认知缺陷。γ-氨基丁酸（GABA）受体产生的阶段性和持续性抑制调节神经活动，并有助于在支持正常认知的皮质回路中建立适当的网络动态。本综述重点介绍了表明抑制性信号在衰老过程中发生改变的基础科学，并讨论了与年龄相关的抑制变化对不同形式记忆功能的影响，包括海马体依赖的空间参考记忆和前额叶皮质（PFC）依赖的工作记忆。还讨论了针对介导抑制的受体的认知衰老选择性治疗候选药物的临床适用性和可治疗性。
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