Melatonin promotes regeneration of injured motor axons via MT1 receptors

J Pineal Res. 2021 Jan;70(1):e12695. doi: 10.1111/jpi.12695. Epub 2020 Sep 30.

Abstract

Melatonin is an ancient multi-tasking molecule produced by the pineal gland and by several extrapineal tissues. A variety of activities has been ascribed to this hormone in different physiological and pathological contexts, but little is known about its role in peripheral neuroregeneration. Here, we have exploited two different types of injury to test the capability of melatonin to stimulate regeneration of motor axons: (a) the acute and reversible presynaptic degeneration induced by the spider neurotoxin α-Latrotoxin and (b) the compression/transection of the sciatic nerve. We found that in both cases melatonin administration accelerates the process of nerve repair. This pro-regenerative action is MT1 -mediated, and at least in part due to a sustained activation of the ERK1/2 pathway. These findings reveal a receptor-mediated, pro-regenerative action of melatonin in vivo that holds important clinical implications, as it posits melatonin as a safe candidate molecule for the treatment of a number of peripheral neurodegenerative conditions.

Keywords: MT1 and MT2 receptors; Schwann cells; melatonin; neuromuscular junction; peripheral nerve regeneration; sciatic nerve injury; α-Latrotoxin.

MeSH terms

  • Animals
  • Axons / drug effects*
  • Axons / metabolism
  • Axons / pathology
  • Cells, Cultured
  • Disease Models, Animal
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Melatonin / pharmacology*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Motor Neurons / drug effects*
  • Motor Neurons / metabolism
  • Motor Neurons / pathology
  • Nerve Regeneration / drug effects*
  • Peripheral Nerve Injuries / drug therapy*
  • Peripheral Nerve Injuries / metabolism
  • Peripheral Nerve Injuries / pathology
  • Phosphorylation
  • Rats
  • Rats, Wistar
  • Receptor, Melatonin, MT1 / agonists*
  • Receptor, Melatonin, MT1 / metabolism
  • Sciatic Nerve / drug effects*
  • Sciatic Nerve / injuries
  • Sciatic Nerve / metabolism
  • Sciatic Nerve / pathology
  • Signal Transduction
  • Spider Venoms / toxicity
  • Time Factors

Substances

  • Receptor, Melatonin, MT1
  • Spider Venoms
  • alpha-latrotoxin
  • Extracellular Signal-Regulated MAP Kinases
  • Melatonin