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−1 for 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.
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Acknowledgements
This work was supported by grants from the National Natural Science Foundation of China (No 81273497; 81573413), the Program for Changjiang Scholars and Innovative Research Team in University (No IRT1193), and the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
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Lin, Jr., Fang, Sc., Tang, Ss. et al. Hippocampal CysLT1R knockdown or blockade represses LPS-induced depressive behaviors and neuroinflammatory response in mice. Acta Pharmacol Sin 38, 477–487 (2017). https://doi.org/10.1038/aps.2016.145
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DOI: https://doi.org/10.1038/aps.2016.145
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