以代谢因子为抑郁症治疗靶点在中药抗抑郁单体开发中的应用

Application of Metabolic Factors as Targets in Exploring Antidepressant Traditional Chinese Medicine Monomers

由于缺乏对抑郁症发病机制的系统认识,对抑郁症的治疗和防控目前仍集中于缓解患者神经精神病理改变。越来越多的研究发现,成年海马神经新生是一种特有的神经可塑性,参与了人体对心理压力应激的生物过程。增加海马神经新生是一种有效的抑郁症治疗手段。代谢因子异常在神经精神类疾病发生发展中的作用已被广泛证实。研究代谢因子在调控神经新生方面的功能能够为寻找抗抑郁药物提供新的治疗靶点。该文总结了各类代谢因子对神经新生的调控,探讨了这些代谢因子作为抗抑郁治疗靶点的可能性。同时,介绍代谢因子APPL2对海马神经新生及对动物抗抑郁行为的调控效应及其机制。以APPL2为靶点,中药单体黄芩苷能够上调抑郁症状态下海马及嗅觉区域神经新生水平,并且能够缓解抑郁焦虑行为及嗅觉功能障碍。该研究表明,代谢因子因其神经新生调控作用可以成为有效的抗抑郁靶点,证实以此为靶点从而开发有效的具有抗抑郁功能的中药单体的可能性。

Because of limit knowledge for biological underpinning of depression,current antidepressant mainly focuses on attenuating the pathological changes and neuropsychiatric symptoms.Emerging evidence indicates the importance of adult hippocampal neurogenesis in regulating the adaptability to psychiatric or psychological stress.Additionally,increasing hippocampal neurogenesis is an effective approach for antidepressant therapy.Abnormalities of metabolic factors in contributing the development of neurological or psychiatric diseases have been widely documented.Investigating the function of metabolic factors could offer the new target for antidepressants exploration.In this review,we summarized the functions of different types of metabolic factors in regulating neurogenesis as well as the possibility of these factors as the antidepressant targets.Meanwhile,we introduced the previous work in our laboratory:the roles of metabolic factor APPL2 in regulating adult hippocampal neurogenesis and antidepressant behaviors.By targeting APPL2,baicalin could exert the neurogenic promotion in hippocampus and olfactory system and thereby attenuate the emotional and olfactory dysfunctions in depression model.This case offers the significance of metabolic factor as the effective targets in regulating neurogenesis and antidepressant.Moreover,by targeting these identified metabolic factors,many types of traditional Chinese medicine monomers may be applied as the effective antidepressants.