title: Knockdown of hippocampal cysteinyl leukotriene receptor 1 prevents depressive behavior and neuroinflammation induced by chronic mild stress in mice.
abstract: BACKGROUND
  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.
  
  
  OBJECTIVE
  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.affiliation: 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.
authors.forename: Xu-Ben
authors.initials: XB
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Rong-Rong
authors.initials: RR
authors.lastname: Dong
authors.affiliation: Department of Medical Technology, Taizhou Polytechnic College, Taizhou, 225300, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: 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.
authors.forename: Jing-Ran
authors.initials: JR
authors.lastname: Lin
authors.affiliation: 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.
authors.forename: Yun-Qi
authors.initials: YQ
authors.lastname: An
authors.affiliation: 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.
authors.forename: Yong
authors.initials: Y
authors.lastname: Du
authors.affiliation: 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.
authors.forename: Su-Su
authors.initials: SS
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Mei
authors.initials: M
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Yan
authors.initials: Y
authors.lastname: Long
authors.affiliation: 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.
authors.forename: Hong-Bin
authors.initials: HB
authors.lastname: Sun
authors.affiliation: 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.
authors.forename: Ling-Yi
authors.initials: LY
authors.lastname: Kong
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
mesh_terms: D000818:Animals; D018687:Antidepressive Agents, Second-Generation / Q000494:pharmacology; D001007:Anxiety / Q000523:psychology; D016207:Cytokines / Q000378:metabolism; D003863:Depression / Q000209:etiology* / Q000235:genetics*; D004435:Eating / Q000187:drug effects; D005473:Fluoxetine / Q000494:pharmacology; D055785:Gene Knockdown Techniques; D019417:Hindlimb Suspension / Q000523:psychology; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism*; D007249:Inflammation / Q000150:complications* / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D018077:Receptors, Leukotriene / Q000235:genetics*; D013315:Stress, Psychological / Q000378:metabolism* / Q000523:psychology*
chemical_list: D018687:Antidepressive Agents, Second-Generation; D016207:Cytokines; D018077:Receptors, Leukotriene; D005473:Fluoxetine; C083169:leukotriene D4 receptor
keywords: Chronic mild stress; Cysteinyl leukotriene receptor 1; Depression; Neuroinflammation