摘要
海马糖皮质激素受体(GR)参与下丘脑-垂体-肾上腺(HPA)轴功能的负反馈调节,是调控机体应激反应和海马可塑性不可或缺的因素。海马GR可以通过抑制HPA轴关键调节因子促肾上腺皮质激素释放激素(CRH)的转录与合成,实现对HPA轴的负反馈调节,从而促进应激后机体内稳态恢复。但GR长期过度激活将损害海马突触可塑性,影响学习记忆功能。GR拮抗剂可以抑制GR功能,起到拮抗糖皮质激素、抑制神经炎症、减轻海马细胞凋亡等效果,但可能引起HPA轴负反馈功能减弱。FK506结合蛋白5可调节GR的敏感性,以其为靶标的药物可以调节HPA轴的活性。如何控制应激时GR的表达异常,而不影响GR对HPA轴的负反馈值得进一步研究。
Hippocampus glucocorticoid receptor(GR) plays a negative regulatory role in the hypothalamic pituitary adrenal(HPA) axis. It is believed that GR is essential in the regulation of the stress response and hippocampal plasticity. Hippocampal GR could inhibit the transcription and synthesis of corticotropin-releasing hormone(CRH), a vital regulator of the HPA axis, to achieve negative regulation of the HPA axis, thereby normalizing homeostasis after stress. However, overactivation of GR modifies synaptic plasticity, subsequently damages learning and memory function. Antagonists of GR antagonize glucocorticoids, inhibit neuroinflammation, and reduce hippocampal cell apoptosis, while GR antagonists may reduce GR negative feedback on the HPA axis. Given that FK506 binding protein 5(FKBP5) suppresses GR translocation, drugs targeting FKBP5 can effectively regulate the HPA axis activity. How to regulate the abnormal expression of GR during stress without affecting the negative feedback function of GR on the HPA axis is worthy of further study.
作者
王钰
田占庄
WANG Yu;TIAN Zhan-zhuang(Department of Integrative Medicine and Neurobiology,School of Basic Medical Sciences,Fndan Unwersity/Academy of Integrative Medicine,Fndan University/Ins tiMe of Acupuncture Research,Medical College,Fudart University,SHANGHAI 200032,China)
出处
《中国新药与临床杂志》
CAS
CSCD
北大核心
2021年第4期241-246,共6页
Chinese Journal of New Drugs and Clinical Remedies
基金
国家自然科学基金(81973639,8157140418)。
