Melatonin exerts neuroprotective effects in mice with spinal cord injury by activating the Nrf2/Keap1 signaling pathway via the MT2 receptor

Spinal cord injury (SCI) is a devastating event that often leads to severe disability, and effective treatments for SCI are currently limited. The present study investigated the potential effects and specific mechanisms of melatonin treatment in SCI. Melatonin treatment alleviated the severity of spinal injuries and facilitated functional recovery in mice with SCI. Notably, blocking MT2 with 4P‑PDOT partially reversed the neuroprotective effects of melatonin in SCI, indicating that the activation of the MT2/Nrf2/Keap1 signaling pathway contributes to the neuroprotective properties of melatonin in SCI. The therapeutic and translational potentials of melatonin in SCI warrant further investigation.

• 1
  Melatonin increased the expression of the MT2 receptor and activated the Nrf2/Keap1 signal pathway.
• 2
  Melatonin reduced neuronal death and increased neuronal survival through MT2 receptor activation.
• 3
  Melatonin promoted the recovery of hindlimb motor function in SCI mice through MT2 receptor activation.