Maruyama Yoshiaki, Yamada Mitsuhiko
Department of Psychogeriatrics, National Institute of Mental Health, National Center of Neurology and Psychiatry, Kodaira, Japan.
Nihon Shinkei Seishin Yakurigaku Zasshi. 2007 Aug;27(4):147-51.
The neurotransmitter serotonin (5-HT: 5-hydroxytryptamin) was suggested to be involved in the pathogenesis of depression as well as in the mechanisms of antidepressant treatments. However, the molecular mechanisms underlying the pathophysiology or treatment of depression are still poorly understood. A recent paper has shown that deletion of the two-pore domain potassium channel TREK-1 results in an antidepressant-like phenotype. TREK-1 -deficient mice behave as if they have been treated with an antidepressant drug, such as fluoxetine. Moreover, TREK-1-deficient mice showed a reduced elevation of corticosterone level under stress, an increased efficacy of 5-HT neurotransmission and an increased fluoxetine-induced neurogenesis in the hippocampus. Selective serotonin reuptake inhibitors (SSRIs) inhibited not only the 5-HT transporter but also the TREK-1 channel. In this article, we review the molecular and functional properties of the TREK-1 channel, which is a potential target for novel antidepressants.
神经递质5-羟色胺（5-HT：5-羟色胺）被认为与抑郁症的发病机制以及抗抑郁治疗机制有关。然而，抑郁症病理生理学或治疗背后的分子机制仍知之甚少。最近一篇论文表明，双孔结构域钾通道TREK-1的缺失会导致抗抑郁样表型。TREK-1基因敲除小鼠的行为表现就好像它们已经接受了抗抑郁药物（如氟西汀）的治疗。此外，TREK-1基因敲除小鼠在应激状态下皮质酮水平的升高有所降低，5-羟色胺神经传递效率增加，并且氟西汀诱导的海马神经发生增加。选择性5-羟色胺再摄取抑制剂（SSRIs）不仅抑制5-羟色胺转运体，还抑制TREK-1通道。在本文中，我们综述了TREK-1通道的分子和功能特性，它是新型抗抑郁药的潜在靶点。
