Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
Hippocampus. 2009 Nov;19(11):1130-41. doi: 10.1002/hipo.20576.
There is an increasing body of evidence suggesting that GABAergic dysfunction is involved in various psychiatric disorders. The goal of our study was to investigate the influences of electroconvulsive therapy (ECT), one of the most effective treatments for depression, on the GABAergic system in the hippocampus. In this stereology-based study, we identified GABAergic neurons by immunostaining for two isoforms of glutamic acid decarboxylase (GAD), GAD65, and GAD67 and estimated the expression changes induced by single or repeated electroconvulsive shock (ECS; an animal model of ECT). The numerical density (ND) of entire population of GABAergic neurons (expressing GAD65 and/or GAD67) was seldom altered by the administration of ECS. GAD67-positive (GAD67(+)) neurons were also rarely affected by ECS. On the other hand, the ND of GAD65(+) neurons was changed in a layer-specific manner. In the CA1 region, the ND of GAD65(+) neurons was increased in the strata radiatum/lacunosum-moleculare (SR/SLM) by repeated ECS. In the CA3 region, the ND of GAD65(+) neurons was decreased in the stratum oriens and SR/SLM after single ECS. The expression ratio of GAD65 in GABAergic neurons was increased specifically in layers receiving afferents from the entorhinal cortex (EC), i.e., SR/SLM of the CA1 region and molecular layer of the dentate gyrus (DG), after repeated ECS administration, whereas the expression ratio of GAD67 in GABAergic neurons was decreased in several layers by the same treatment. These results indicate that the ECS-induced changes in ND of GAD65(+) or GAD67(+) neurons were most likely due to alterations in GAD expression rather than actual increases or decreases in cell numbers. Altogether, the neuronal circuit-dependent alterations in GABA-mediated signaling may play a contributory role in the depression treatment process introduced by ECT.
越来越多的证据表明，GABA 能神经功能障碍与各种精神疾病有关。我们的研究目的是探讨电惊厥疗法（ECT）——一种治疗抑郁症最有效的方法之一——对海马 GABA 能系统的影响。在这项基于体视学的研究中，我们通过免疫染色两种谷氨酸脱羧酶（GAD）同工型（GAD65 和 GAD67）来鉴定 GABA 能神经元，并估计单次或重复电惊厥刺激（ECT 的动物模型）引起的表达变化。整个 GABA 能神经元（表达 GAD65 和/或 GAD67）群体的数量密度（ND）很少受到 ECS 给药的影响。GAD67 阳性（GAD67(+)）神经元也很少受到 ECS 的影响。另一方面，GAD65(+)神经元的 ND 以层特异性的方式发生变化。在 CA1 区，重复 ECS 增加了放射层/腔隙分子层（SR/SLM）中 GAD65(+)神经元的 ND。在 CA3 区，单次 ECS 后，GAD65(+)神经元在始层和 SR/SLM 的 ND 减少。在重复 ECS 给药后，GAD65 在 GABA 能神经元中的表达比例在特定的接受来自内侧隔核（EC）传入的层中增加，即 CA1 区的 SR/SLM 和齿状回的分子层（DG），而 GABA 能神经元中的 GAD67 表达比例在同一处理后在几个层中降低。这些结果表明，GAD65(+)或 GAD67(+)神经元 ND 的 ECS 诱导变化很可能是由于 GAD 表达的改变，而不是细胞数量的实际增加或减少。总的来说，GABA 介导的信号转导的神经元回路依赖性改变可能在 ECT 引入的抑郁症治疗过程中发挥作用。
