Knockdown of hippocampal cysteinyl leukotriene receptor 1 prevents depressive behavior and neuroinflammation induced by chronic mild stress in mice

Numerous studies have demonstrated that neuroinflammation is associated with depression-like symptoms and neuropsychological disturbances, and cysteinyl leukotriene receptor 1 (CysLT(1)R) was reported to be involved in neuroinflammation. The pathophysiological role of CysLT(1)R has been reported in several types of brain damage. However, the role of CysLT(1)R in depression remains to be elucidated. We aimed to investigate the effect of hippocampal CysLT(1)R downregulation on depressive behaviors and neuroinflammatory responses in mice exposed to chronic mild stress (CMS). We firstly found that expression of hippocampal CysLT(1)R was gradually increased over CMS exposure, while 3 weeks treatment with fluoxetine reversed the increment of hippocampal CysLT(1)R expression. Hippocampal CysLT(1)R 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-kappa B p65, IL-1 beta, and TNF-alpha induced by CMS were also prevented by hippocampal CysLT(1)R knockdown beforehand. Hippocampal CysLT(1)R participates in depression, and knockdown of hippocampal CysLT(1)R prevents CMS-induced depressive-like behaviors and neuroinflammation, suggesting that suppression of CysLT(1)R could prevent the development of depression.