Cui Yihui, Yang Yan, Dong Yiyan, Hu Hailan
Center for Neuroscience and Department of Psychiatry of First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310058, China.
NHC and CAMS Key Laboratory of Medical Neurobiology, Zhejiang University, Hangzhou 310058, China.
Cold Spring Harb Symp Quant Biol. 2018;83:141-150. doi: 10.1101/sqb.2018.83.036871. Epub 2019 Feb 4.
The rapid antidepressant effect of ketamine is arguably one of the most significant advances in the mental health field in the last half century. However, its mechanism of action has remained elusive. Here, we describe our latest discovery on how ketamine blocks -methyl-D-aspartate receptor (NMDAR)-dependent burst firing of an "antireward" center in the brain, the lateral habenula (LHb), to mediate its antidepressant effects. We also discuss a novel structure-function mechanism at the glia-neuron interface to account for the enhanced LHb bursting during depression. These results reveal new molecular targets for the therapeutic intervention of major depression.
氯胺酮的快速抗抑郁作用可以说是过去半个世纪精神健康领域最重要的进展之一。然而，其作用机制一直难以捉摸。在此，我们描述了我们的最新发现，即氯胺酮如何阻断大脑中一个“抗奖赏”中心——外侧缰核（LHb）依赖于N-甲基-D-天冬氨酸受体（NMDAR）的爆发式放电，以介导其抗抑郁作用。我们还讨论了神经胶质细胞与神经元界面处一种新的结构-功能机制，以解释抑郁症期间LHb爆发式放电增强的原因。这些结果揭示了重度抑郁症治疗干预的新分子靶点。
