毒蕈碱型胆碱受体与抑郁症

Muscarinic acetylcholine receptor and depression

毒蕈碱型乙酰胆碱受体(muscarinic acetylcholine receptor,M-AChR)是胆碱能受体的一种,近年来关于各类M-AChR在抑郁症中的机制研究很多,本次主要对M-AChR在抑郁症发病和治疗中的相关机制进行阐述和总结,并且对相关药物的研究进行总结和展望。M1-AChR、M2-AChR在抗抑郁方面发挥重要作用,其可能机制涉及海马和前额叶皮质(prefrontal cortex,PFC)等脑区雷帕霉素靶蛋白复合体1(mammalian target of rapamycin complex 1,mTORC1)信号通路的激活、兴奋性神经递质和脑源性神经营养因子(brain-derived neurotrophic factor,BDNF)等因子的释放等,同时蛋白激酶A(protein kinase A,PKA)-α-氨基羟甲基恶唑丙酸(α-amino-3-hydroxy-5-methylisoxazole-4-propionieacid,AMPA)通路的激活在M2-AChR介导的抗抑郁效应中起重要调节作用,但是具体机制以及各类M-AChR间的相互作用仍有待于探究,这也可能成为接下来的研究重点。目前,相关药物的临床试验主要集中在东莨菪碱,随着临床试验的进展,该药物的量效曲线和副作用耐受性等会更加明确,相信更多患者能够从中受益。

Muscarinic acetylcholine receptor(M-AChR)is a type of cholinergic receptor.In recent years,there have been many studies on the mechanism of various types of M-AChR in depression.Therefore,this review intends to focus on M-AChR related mechanisms in the onset and treatment of depression,and the research of related drugs is summarized and prospected.The results show that M1-AChR and M2-AChR play important roles in antidepressant,and its possible mechanism involves the mammalian target of rapamycin complex 1(mTORC1)signal pathway activation in the hippocampus and prefrontal cortex(PFC),release of excitatory neurotransmitter and brain-derived neurotrophic factor(BDNF)and other factors,at the same time protein kinase A-α-amino the activation of theα-amino-3-hydroxy-5-methylisoxazole-4-propionieacid(AMPA)pathway plays an important regulatory role in the antidepressant effect mediated by M2-AChR,but the specific mechanisms and the interactions between various type of M-AChR are still to be explored,which may also become the focus of future research.At present,clinical trials of related drugs are mainly focused on scopolamine.With the progress of clinical trials,the dose-effect curve and side effects tolerance of scopolamine will be more clearly and it is believed that more patients can benefit from it.