Abstract

BACKGROUND: The aim of this study was to explore the effect of metformin by inducing autophagy for enhancing functional recovery of peripheral nerve in rats with sciatic nerve crush injury.

MATERIAL AND METHODS: Autophagy was determined by electron microscopy, immunofluorescence, and Western blot analysis. Motor function recovery was studied by the footprint intensity method. Axonal growth and regeneration were detected through Western blot while axonal remyelination was analysed through immunocytochemistry. Sensory and functional recovery were assessed by reflexive motor function analysis.

RESULTS: The present study deciphered the role of autophagy induction by metformin in motor functions and peripheral nerve regeneration following sciatic nerve crush injury in rats. The process was detected by measuring autophagosomes and the expression of microtubule-associated protein 1A/1B-light chain 3 upon metformin treatment of sciatic nerve crush-injured rats. Neurobehavioral recovery by metformin was tested by CatWalk gait analysis, and we quantified expression of myelin basic protein MBP and neurofilament NF200 at the damage sight by immunoblotting. In metformin-treated injured rats, autophagy was upregulated, by which the number of dead cells was decreased. Motor function was also recovered after metformin treatment, which was accompanied by upregulation of MBP and NF200 through autophagy induction. Surprisingly, the motor regenerative capability was reduced by treatment with 3-methyl adenine (an autophagy inhibitor) in nerve-injured rats.

CONCLUSIONS: Our study revealed that pharmacological induction of autophagy has an important and active role in the regeneration of nerve and motor function regain.

Keywords: Metformin, Sciatic Nerve, Axons, Crush Injuries, Mice, Inbred C57BL, Motor Activity, myelin basic protein, Nerve Crush, Nerve Regeneration, Neural Conduction, Neurofilament Proteins, Recovery of Function, Up-Regulation