哺乳动物西罗莫司靶蛋白信号通路在氯胺酮抗抑郁作用中的研究进展

Research Progress of the m TOR Signaling Pathway Underlying the Antidepressant Actions of Ketamine

抑郁症严重危害人类身心健康。目前,抗抑郁药物存在初始治疗有效率低、起效慢、无法快速缓解抑郁症患者的痛苦等缺陷。研究发现,氯胺酮对难治型抑郁症患者有快速抗抑郁作用。动物模型的分子生物学和细胞学研究表明,氯胺酮通过激活哺乳动物西罗莫司靶蛋白(mammalian target of rapamycin,m TOR)信号通路来激发哺乳动物西罗莫司靶蛋白及其下游分子的翻译起始过程,从而增加前额叶皮层棘突突触的成熟度和数量,达到抑郁症治疗的目的。这些研究提示哺乳动物西罗莫司靶蛋白信号通路在氯胺酮快速抗抑郁作用中发挥重要作用,其在探索新型高效抗抑郁药物中具有巨大的潜力。

Depression is a common, serious psychiatric disease. Despite a wide range of antidepressants available, only one third of the patients show significant mood improvement in response to an initial antidepressant treatment. Moreover, there is a time-lag of weeks to months with currently available medications; the suffering of patients could not be relieved quickly. Ketamine was found to produce rapid antidepressant responses in treatment resistant major depressive disorder patients. Molecular and cellular studies in rodent models demonstrated that ketamine stimulates mammalian target of rapamyein （roTOR） signaling and increases the initial translation of mTOR and downstream molecules, these effects of ketamine are accompanied by increasing levels of maturity and quantity of spine synapses in the prefrontal cortex. Ketamine was found to produce rapid antidepressant responses in treatment of depression. These studies identify the characterization of the roTOR signaling pathway in depression and its action in response to antidepressants shows great potential for the identification of new therapeutic targets for the development of antidepressant drugs.