title: Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice.
abstract: Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLT1R) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLT1R in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLT1R knockdown and CysLT1R blockade on LPS-induced depressive-like behavior in mice. We found that injection of LPS (0.5 mg/kg, ip) caused marked increase in hippocampal CysLT1R expression, which was reversed by pretreatment with fluoxetine (20 mg·kg-1·d-1for 7 d, ig). Knockdown of hippocampal CysLT1R or blockade of CysLT1R by pretreatment with pranlukast (0.5 mg/kg, ip) significantly suppressed LPS-induced depressive behaviors, as evidenced by decreases in mouse immobility time in the forced swimming test (FST) and tail suspension test (TST) and latency to feed in the novelty-suppressed feeding (NSF) test. Moreover, both CysLT1R knockdown and CysLT1R blockade markedly prevented LPS-induced neuroinflammation, as shown by the suppressed activation of microglia and NF-κB signaling as well as the hippocampal levels of TNF-α and IL-1β in mice. Our results suggest that CysLT1R may be involved in LPS-induced depressive-like behaviors and neuroinflammation, and that downregulation of CysLT1R could be a novel and potential therapeutic strategy for the treatment of depression, at least partially due to its role in neuroinflammation.
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: Shun-Chang
authors.initials: SC
authors.lastname: Fang
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: Arijit
authors.initials: A
authors.lastname: Ghosh
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.
authors.forename: Hao
authors.initials: H
authors.lastname: Hong
mesh_terms: D000818:Animals; D002867:Chromones / Q000627:therapeutic use; D003863:Depression / Q000188:drug therapy* / Q000378:metabolism / Q000523:psychology; D005473:Fluoxetine / Q000627:therapeutic use; D055785:Gene Knockdown Techniques; D006624:Hippocampus / Q000378:metabolism*; D007249:Inflammation / Q000188:drug therapy / Q000378:metabolism; D020024:Leukotriene Antagonists / Q000627:therapeutic use; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D008813:Mice, Inbred ICR; D018077:Receptors, Leukotriene / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction
chemical_list: D002867:Chromones; D020024:Leukotriene Antagonists; D008070:Lipopolysaccharides; D018077:Receptors, Leukotriene; D005473:Fluoxetine; C083169:leukotriene D4 receptor; C047681:pranlukast