Hippocampal CysLTR knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice.

Evidence suggests that neuroinflammation is involved in depression and that the cysteinyl leukotriene receptor 1 (CysLTR) plays a potential pathophysiological role in several types of CNS disorders. Our previous study has shown that knockdown of hippocampal CysLTR in mice prevents the depressive-like phenotype and neuroinflammation induced by chronic mild stress (CMS). Here, we examined the effects of hippocampal CysLTR knockdown and CysLTR 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 CysLTR expression, which was reversed by pretreatment with fluoxetine (20 mg·kg·d for 7 d, ig). Knockdown of hippocampal CysLTR or blockade of CysLTR 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 CysLTR knockdown and CysLTR 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 CysLTR may be involved in LPS-induced depressive-like behaviors and neuroinflammation, and that downregulation of CysLTR could be a novel and potential therapeutic strategy for the treatment of depression, at least partially due to its role in neuroinflammation.