Inhibition of acid-sensing ion channels reduces the hypothalamus-pituitary-adrenal axis activity and ameliorates depression-like behavior in rats

被引：10
作者：
Zhou, Wenjie [1 ]
Ye, Shandong [2 ]
Luo, Rong [3 ]
Wu, Li-Min [4 ]
Wang, Wei [2 ]
机构：
[1] Univ Sci & Technol China, Key Lab Brain Funct & Dis, Hefei Natl Lab Phys Sci Microscale, Hefei 230027, Anhui, Peoples R China
[2] Univ Sci & Technol China, Div Life Sci & Med, Affiliated Hosp 1, Dept Endocrinol, Hefei 230001, Anhui, Peoples R China
[3] Capital Med Univ, Sch Tradit Chinese Med, Beijing 100069, Peoples R China
[4] Univ Sci & Technol China, Div Life Sci & Med, Affiliated Hosp 1, Ctr Reprod Med, Hefei 230001, Anhui, Peoples R China
来源：
RSC ADVANCES | 2019年 / 9卷 / 16期
基金：
中国国家自然科学基金;
关键词：
MAJOR DEPRESSION; MILD STRESS; LATERAL HABENULA; DRUG DISCOVERY; RISK-FACTOR; HPA AXIS; MODEL; RECEPTORS; AMILORIDE; RESPONSES;
D O I：
10.1039/c9ra00020h
中图分类号：
O6 [化学];
学科分类号：
0703 ;
摘要：
Depression is the leading cause of disability worldwide, and its treatment represents a major clinical challenge. The hypothalamus-pituitary-adrenal (HPA) axis has been known to play a crucial role in depression and serves as a target for antidepressants. Acid-sensing ion channels (ASICs) are widely expressed in the nervous system and may be implicated in depression. Whether ASICs could act on the HPA axis to affect depression-related behaviors is not fully understood. In this study, we investigated the effect of inhibition of ASICs on the HPA axis activity in chronic stress-subjected rats. We found that treatment with the ASIC selective antagonist amiloride reversed chronic stress-induced elevation of adrenocorticotropic hormone (ACTH) and corticosterone in serum, which is reflective of the HPA axis activity. In addition, amiloride also alleviated chronic stress-induced anhedonia-like behavior. These results suggest that inhibition of ASICs may act on the HPA axis to alleviate the symptoms of depression.
引用
收藏
页码：8707 / 8713
页数：7
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