A Multiscale View of the Mechanisms Underlying Ketamine's Antidepressant Effects: An Update on Neuronal Calcium Signaling.
A Multiscale View of the Mechanisms Underlying Ketamine's Antidepressant Effects: An Update on Neuronal Calcium Signaling.
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DOI：
10.3389/fnbeh.2021.749180
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发表时间：
2021
影响因子：
3
通讯作者：
Uchida S
中科院分区：
文献类型：
--
作者：
Kawatake-Kuno A;Murai T;Uchida S
严重抑郁障碍(MDD)是一种衰弱的疾病，其特征是情绪低落，失去兴趣或快乐，有自杀念头，动力减弱或绝望。尽管进行了大量研究，但MDD的潜在机制仍然知之甚少，目前的治疗进展也远远不能令人满意。氯胺酮的抗抑郁作用是过去半个世纪精神病学研究中最重要的发现之一。对氯胺酮作用的神经生物学洞察力揭示了抗抑郁药物疗效的潜在机制。然而，氯胺酮快速而持久的抗抑郁作用的机制仍然存在争议。阐明这些机制是确定新的治疗靶点和开发治疗策略的关键。越来越多的证据表明，中枢神经系统中主要的兴奋性神经递质系统谷氨酸能通路在MDD的病理生理和抗抑郁作用中起着重要作用。谷氨酸能系统刺激的钙信号级联、神经可塑性和基因转录的表观遗传调控之间存在联系的假说，与氯胺酮的抗抑郁作用有关，进一步支持了这一假说。本文从行为、细胞、分子和表观遗传学等多个角度对氯胺酮的潜在作用机制进行了简要综述，重点介绍了谷氨酸能信号转导机制，为氯胺酮的抗抑郁作用提供了有价值的综述。
Major depressive disorder (MDD) is a debilitating disease characterized by depressed mood, loss of interest or pleasure, suicidal ideation, and reduced motivation or hopelessness. Despite considerable research, mechanisms underlying MDD remain poorly understood, and current advances in treatment are far from satisfactory. The antidepressant effect of ketamine is among the most important discoveries in psychiatric research over the last half-century. Neurobiological insights into the ketamine’s effects have shed light on the mechanisms underlying antidepressant efficacy. However, mechanisms underlying the rapid and sustained antidepressant effects of ketamine remain controversial. Elucidating such mechanisms is key to identifying new therapeutic targets and developing therapeutic strategies. Accumulating evidence demonstrates the contribution of the glutamatergic pathway, the major excitatory neurotransmitter system in the central nervous system, in MDD pathophysiology and antidepressant effects. The hypothesis of a connection among the calcium signaling cascade stimulated by the glutamatergic system, neural plasticity, and epigenetic regulation of gene transcription is further supported by its associations with ketamine’s antidepressant effects. This review briefly summarizes the potential mechanisms of ketamine’s effects with a specific focus on glutamatergic signaling from a multiscale perspective, including behavioral, cellular, molecular, and epigenetic aspects, to provide a valuable overview of ketamine’s antidepressant effects.
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