Zhou Wenjie, Ye Shandong, Luo Rong, Wu Li-Min, Wang Wei
Hefei National Laboratory for Physical Sciences at the Microscale, Key Laboratory of Brain Function and Disease, University of Science and Technology of China Hefei 230027 PR China.
Department of Endocrinology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China Hefei Anhui 230001 P. R. China
RSC Adv. 2019 Mar 15;9(16):8707-8713. doi: 10.1039/c9ra00020h.
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.
抑郁症是全球导致残疾的主要原因，其治疗是一项重大的临床挑战。已知下丘脑-垂体-肾上腺（HPA）轴在抑郁症中起关键作用，并作为抗抑郁药的作用靶点。酸敏感离子通道（ASICs）在神经系统中广泛表达，可能与抑郁症有关。ASICs是否可作用于HPA轴以影响与抑郁相关的行为尚不完全清楚。在本研究中，我们研究了抑制ASICs对慢性应激大鼠HPA轴活性的影响。我们发现，用ASIC选择性拮抗剂氨氯吡咪治疗可逆转慢性应激诱导的血清促肾上腺皮质激素（ACTH）和皮质酮升高，这反映了HPA轴的活性。此外，氨氯吡咪还减轻了慢性应激诱导的快感缺失样行为。这些结果表明，抑制ASICs可能作用于HPA轴以减轻抑郁症状。
