Xu-Ben Yu1, Rong-Rong Dong1, Hui Wang2, Jing-Ran Lin1, Yun-Qi An1, Yong Du1, Su-Su Tang1, Mei Hu1, Yan Long1, Hong-Bin Sun1, Ling-Yi Kong1, Hao Hong3. 1. Department of Pharmacology, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. 2. Department of Medical Technology, Taizhou Polytechnic College, Taizhou, 225300, China. 3. Department of Pharmacology, Jiangsu Key Laboratory of Drug Discovery for Metabolic Diseases, and State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing, 210009, China. honghao@cpu.edu.cn.
Abstract
RATIONALE: Numerous studies have demonstrated that neuroinflammation is associated with depression-like symptoms and neuropsychological disturbances, and cysteinyl leukotriene receptor 1 (CysLT1R) was reported to be involved in neuroinflammation. The pathophysiological role of CysLT1R has been reported in several types of brain damage. However, the role of CysLT1R in depression remains to be elucidated. OBJECTIVES: We aimed to investigate the effect of hippocampal CysLT1R downregulation on depressive behaviors and neuroinflammatory responses in mice exposed to chronic mild stress (CMS). RESULTS: We firstly found that expression of hippocampal CysLT1R was gradually increased over CMS exposure, while 3 weeks treatment with fluoxetine reversed the increment of hippocampal CysLT1R expression. Hippocampal CysLT1R knockdown suppressed CMS-induced depressive-like behaviors as evidenced by decreases in immobility time in tail suspension test (TST), decreased latency to feed in novelty-suppressed feeding (NSF) test, and by increase in the number of entries and decrease in time spent in the open arm in elevated plus maze (EPM) test. Increments of hippocampal NF-κB p65, IL-1β, and TNF-α induced by CMS were also prevented by hippocampal CysLT1R knockdown beforehand. CONCLUSIONS: Hippocampal CysLT1R participates in depression, and knockdown of hippocampal CysLT1R prevents CMS-induced depressive-like behaviors and neuroinflammation, suggesting that suppression of CysLT1R could prevent the development of depression.
RATIONALE: Numerous studies have demonstrated that neuroinflammation is associated with depression-like symptoms and neuropsychological disturbances, and cysteinyl leukotriene receptor 1 (CysLT1R) was reported to be involved in neuroinflammation. The pathophysiological role of CysLT1R has been reported in several types of brain damage. However, the role of CysLT1R in depression remains to be elucidated. OBJECTIVES: We aimed to investigate the effect of hippocampal CysLT1R downregulation on depressive behaviors and neuroinflammatory responses in mice exposed to chronic mild stress (CMS). RESULTS: We firstly found that expression of hippocampal CysLT1R was gradually increased over CMS exposure, while 3 weeks treatment with fluoxetine reversed the increment of hippocampal CysLT1R expression. Hippocampal CysLT1R knockdown suppressed CMS-induced depressive-like behaviors as evidenced by decreases in immobility time in tail suspension test (TST), decreased latency to feed in novelty-suppressed feeding (NSF) test, and by increase in the number of entries and decrease in time spent in the open arm in elevated plus maze (EPM) test. Increments of hippocampal NF-κB p65, IL-1β, and TNF-α induced by CMS were also prevented by hippocampal CysLT1R knockdown beforehand. CONCLUSIONS: Hippocampal CysLT1R participates in depression, and knockdown of hippocampal CysLT1R prevents CMS-induced depressive-like behaviors and neuroinflammation, suggesting that suppression of CysLT1R could prevent the development of depression.
Authors: Frank Stegmeier; Guang Hu; Richard J Rickles; Gregory J Hannon; Stephen J Elledge Journal: Proc Natl Acad Sci U S A Date: 2005-09-01 Impact factor: 11.205
Authors: Gisele A Locachevic; Morgana K B Prado; Karina F Zoccal; Priscilla A T Pereira; Carlos A Sorgi; Mariza Bortolanza; Ana Paula F Peti; Manoela V Fogaça; Francisco S Guimarães; Elaine Del Bel; Lúcia H Faccioli Journal: Front Behav Neurosci Date: 2019-04-16 Impact factor: 3.558