AUTHOR=Ali Tahir , Hao Qiang , Ullah Najeeb , Rahman Shafiq Ur , Shah Fawad Ali , He Kaiwu , Zheng Chengyou , Li Weifen , Murtaza Iram , Li Yang , Jiang Yuhua , Tan Zhen , Li Shupeng TITLE=Melatonin Act as an Antidepressant via Attenuation of Neuroinflammation by Targeting Sirt1/Nrf2/HO-1 Signaling JOURNAL=Frontiers in Molecular Neuroscience VOLUME=13 YEAR=2020 URL=https://www.frontiersin.org/journals/molecular-neuroscience/articles/10.3389/fnmol.2020.00096 DOI=10.3389/fnmol.2020.00096 ISSN=1662-5099 ABSTRACT=

Physical or psychological stress can cause an immunologic imbalance that disturbs the central nervous system followed by neuroinflammation. The association between inflammation and depression has been widely studied in recent years, though the molecular mechanism is still largely unknown. Thus, targeting the signaling pathways that link stress to neuroinflammation might be a useful strategy against depression. The current study investigated the protective effect of melatonin against lipopolysaccharide (LPS)-induced neuroinflammation and depression. Our results showed that LPS treatment significantly induced depressive-like behavior in mice. Moreover, LPS-treatment enhanced oxidative stress, pro-inflammatory cytokines including TNFα, IL-6, and IL-1β, NF-κB phosphorylation, and glial cell activation markers including GFAP and Iba-1 in the brain of mice. Melatonin treatment significantly abolished the effect of LPS, as indicated by improved depressive-like behaviors, reduced cytokines level, reduced oxidative stress, and normalized LPS-altered Sirt1, Nrf2, and HO-1 expression. However, the melatonin protective effects were reduced after luzindole administration. Collectively, it is concluded that melatonin receptor-dependently protects against LPS-induced depressive-like behaviors via counteracting LPS-induced neuroinflammation.