Department of Neuroscience, Ohio State University, Columbus OH, United States.
Department of Neuroscience, Ohio State University, Columbus OH, United States; Department of Psychology, Ohio State University, Columbus OH, United States.
Neurosci Biobehav Rev. 2019 Oct;105:39-51. doi: 10.1016/j.neubiorev.2019.07.024. Epub 2019 Aug 1.
Chronic stress-induced emotional disorders like anxiety and depression involve imbalances between the excitatory glutamatergic system and the inhibitory GABAergic system in the prefrontal cortex (PFC). However, the precise nature and trajectory of excitatory/inhibitory (E/I) imbalances in these conditions is not clear, with the literature reporting glutamatergic and GABAergic findings that are at times contradictory and inconclusive. Here we propose and discuss the hypothesis that chronic stress-induced emotional dysfunction involves hypoactivity of the PFC due to increased inhibition. We will also discuss E/I imbalances in the context of sex differences. In this review, we will synthesize research about how glutamatergic and GABAergic systems are perturbed by chronic stress and in related emotional disorders like anxiety and depression and propose ideas for reconciling contradictory findings in support of the hypothesis of over-inhibition. We will also discuss evidence for how aspects of the GABAergic system such as parvalbumin (PV) cells can be targeted therapeutically for reinstating activity and plasticity in the PFC and treating stress-related disorders.
慢性应激引起的情绪障碍，如焦虑和抑郁，涉及前额叶皮层 (PFC) 中兴奋性谷氨酸能系统和抑制性 GABA 能系统之间的失衡。然而，这些情况下兴奋性/抑制性 (E/I) 失衡的确切性质和轨迹尚不清楚，文献中报告的谷氨酸能和 GABA 能发现有时相互矛盾且没有定论。在这里，我们提出并讨论了一个假设，即慢性应激引起的情绪功能障碍涉及由于抑制增加而导致的 PFC 活动不足。我们还将在性别差异的背景下讨论 E/I 失衡的问题。在这篇综述中，我们将综合研究慢性应激和相关情绪障碍（如焦虑和抑郁）如何干扰谷氨酸能和 GABA 能系统，并提出一些想法来调和相互矛盾的发现，以支持过度抑制的假说。我们还将讨论 GABA 能系统的某些方面（如 Parvalbumin (PV) 细胞）如何作为治疗靶点，以恢复 PFC 的活动和可塑性，并治疗与应激相关的障碍。
