• Guibin Zhong, Yanqiu Yang, Daming Feng, Ke Wei, Junling Chen, Jianwei Chen, and Chao Deng.
• Department of Orthopaedics, Baoshan Branch, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University, No.1058, Huan Zhen Bei Road, Shanghai 200444, China; Department of Orthopaedics, Ren Ji Hospital, School of Medicine Shanghai Jiao Tong University, Shanghai 200127, China.
• Neuroscience. 2023 Dec 1; 534: 546554-65.

AbstractSpinal cord injuries (SCIs) often result in limited prospects for recovery and a high incidence of disability. Melatonin (Mel), a hormone, is acknowledged for its neuroprotective attributes. Mel was examined in this study to discover if it alleviates SCIs via the sirtuin1/dynamin-related protein1 (SIRT1/Drp1) signaling pathway. SCIs were simulated in mice by inducing cord contusion at the T9-T10 vertebrae and causing inflammation in primary spinal neurons using lipopolysaccharide (LPS). The findings of our study demonstrated that Mel treatment effectively promoted neuromotor recovery through multiple mechanisms, including the reduction of neuronal death, suppression of astrocyte and microglia activation, and attenuation of neuroinflammation. Moreover, Mel therapy significantly upregulated the expression of SIRT1 in both spinal cord tissues and spinal neurons of mice. Additionally, Mel exhibited the potential to mitigate neuronal mitochondrial dysfunction by modulating the levels of Drp1 and TOMM20, thereby addressing the underlying factors contributing to this dysfunction. Furthermore, when SIRT1 was downregulated, it reversed the positive effects of Mel. Overall, our present study suggests that Mel has the capacity to modulate the SIRT1/Drp1 pathway, thereby ameliorating mitochondrial dysfunction, attenuating inflammation and apoptosis, and enhancing neural function subsequent to SCIs.Copyright © 2023 The Authors. Published by Elsevier Ltd.. All rights reserved.

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