Resveratrol attenuates manganese-induced oxidative stress and neuroinflammation through SIRT1 signaling in mice

Exposure to excess levels of manganese (Mn) leads to neurotoxicity. Increasing evidence demonstrates that oxidative stress and neuroinflammation are important pathological causes of neurotoxicity. Resveratrol (Rsv), a sirtuin-1 (SIRT1) activator, plays an important role in neuroprotection. However, the molecular mechanisms of Rsv alleviating Mn-induced oxidative stress and neuroinflammation are not fully understood. To evaluate whether Rsv treatment relieves the oxidative stress and neuroinflammation in the hippocampus after Mn exposure through SIRT1 signaling, C57BL/6 adult mice were exposed to MnCl2 (200 μmol/kg), Rsv (30 mg/kg), and EX527 (5 mg/kg). Our results showed that administering MnCl2 for 6 weeks caused behavioral impairment and nerve cell injury in hippocampal tissue, which was related to oxidative stress and neuroinflammation. Activating Mn-induced JNK and inhibiting SIRT1 increased the phosphorylated and acetylated levels of NF-κB and STAT3, respectively. However, Rsv reduced the phosphorylated and acetylated levels of NF-κB and STAT3, and attenuated Mn-induced oxidative stress and inflammatory cytokines by activating SIRT1 signaling. Most importantly, EX527, a potent SIRT1 inhibitor, inactivated SIRT1, which prevented Rsv from exerting its beneficial effects. Taken together, our findings revealed that Rsv alleviated Mn-induced oxidative stress and neuroinflammation in adult mice by activating SIRT1.