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Bidirectional crosstalk between stress-induced gastric ulcer and depression under chronic stress

 

Shuang Zhang^1,2, Zhiwei Xu¹, Yan Gao¹, Yonghong Wu¹, Zhihui Li¹, Haifeng Liu^2,*, Chenggang Zhang^1,3*

 

¹Beijing Institute of Radiation Medicine, State Key Laboratory of Proteomics, Cognitive and Mental Health Research Center, Beijing 100850, China

²Department of Gastroenterology, the General Hospital of Chinese People’s Armed Police Forces, Beijing 100039, China

³School of Life Science, Anhui Medical University, Anhui, 230032, China

Running title: Crosstalk between gastric ulcer and depression

Abstract

Stress contributes to a variety of diseases and disorders such as depression and peptic ulcer. The present study aimed to investigate the correlation between stress ulcer and depression in pathogenesis and treatment by using chronic stress depression (CSD), chronic psychological stress ulcer (CPSU) and water immersion restrain stress models in rats. Our data showed that the ulcer index of the animals after CSD exposure was significantly higher than that of controls. Depression-like behaviors were observed in rat after CPSU exposure. Fluoxetine hydrochloride significantly reduced the ulcer index of rats exposed to CPSU stress, while ranitidine inhibited depression-like behavior of the animals in CSD group. The ulcer index of rats administered with mifepristone after CPSU stress was markedly reduced compared to CPSU group, although there was no significant difference in the depression-like behavior between mifepristone-treated CSD group and naive controls. We also found that the rats exposed to CPSU or CSD stress displayed a lower level of corticosterone than naive controls, however, the acute stress (AS) group showed an opposite result. Additionally, in order to study the relevance of H₂ receptors and depression, we treated the CSD group with cimetidine and famotidine respectively. The data showed that cimetidine inhibited depression-like behavior in CSD rats, and famotidine had no impact on depression. Overall our data suggested that the hypothalamic-pituitary-adrenal (HPA) axis dysfunction may be the key role in triggering depression and stress ulcer. Acid-suppressing drugs and antidepressants could be used for treatment of depression and stress ulcer respectively. The occurrence of depression might be inhibited by blocking the central H₂ receptors.

Key words: Stress ulcer; Depression; Chronic stress; Acute stress; HPA axis; Histamine H₂-receptor antagonist

应激诱导的胃溃疡和慢性应激导致的抑郁之间的双向交叉对话

摘要

应激可导致包括抑郁和消化性溃疡在内一系列的疾病和生理紊乱。本研究利用慢性应激抑郁（CSD）及慢性心理应激性溃疡（CPSU）大鼠模型来探讨应激性溃疡和抑郁两种疾病在病理机制和治疗上可能存在的相互关系。结果显示：经慢性应激抑郁处理的大鼠，其溃疡指数明显高于对照组，经慢性心理应激性溃疡处理的大鼠表现出明显的抑郁样行为。氟西汀可以明显降低慢性心理应激性溃疡组大鼠的溃疡指数，而雷尼替丁可以抑制慢性应激抑郁组大鼠的抑郁样行为的发生。分别用米非司酮处理慢性心理应激性溃疡组和慢性应激抑郁组，结果显示慢性心理应激性溃疡组大鼠的溃疡指数明显降低，但两组的抑郁样行为和对照组并无差异。我们同时发现慢性心理应激性溃疡组和慢性应激抑郁组大鼠的血清皮质酮水平低于对照组，而急性应激组大鼠的血清皮质酮水平高于对照组。此外，本实验分别用西咪替丁和法莫替丁处理慢性应激抑郁组大鼠，以探讨抑郁样行为的发生与H₂受体之间的关联性。结果显示西咪替丁可以抑制抑郁样行为的发生，但法莫替丁并无此作用。

综上所述，本研究提示HPA轴功能障碍可能在抑郁和应激性溃疡的发病机制中起到关键作用。同时提示抑酸药可能发挥抗抑郁作用，而抗抑郁药可以用于治疗应激性溃疡。阻断中枢H₂受体可能会抑制抑郁的发生。

关键词： 应激性溃疡； 慢性应激； 急性应激； HPA轴； 组胺H2受体拮抗剂

 

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