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.
Highlights
Major depressive disorder (MDD) is a major health concern associated with brain and immune system abnormalities
It was interesting in the report that luzindole treatment significantly abolished melatonin protective effects, suggesting that endogenous melatonin can block the onset of LPS induced depressive-like behaviors
Consistent with the previous reports (Salminen et al, 2008; Luo and Zhang, 2016; Shah et al, 2017), our findings showed that a significant Sirt1 gene suppression in the LPS-treated mice brain, which was improved by melatonin treatment
Summary
Major depressive disorder (MDD) is a major health concern associated with brain and immune system abnormalities. It plays a significant role in the global burden of diseases by affecting people in all communities across the world. Activated peripheral immune system increase cytokines production and flow to CNS, where they induce the activation of astrocytes and microglia, which in turn elevates cytokines production (Muller and Ackenheil, 1998; Song and Wang, 2011). The crosstalk between microglia and astrocytes under stress condition involve in neuroinflammation that leads to dysfunction in the neurotrophic system, which may contribute to the pathogenesis of MDD (Song and Wang, 2011)
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