Metformin Protects Against Spinal Cord Injury by Regulating Autophagy via the mTOR Signaling Pathway

Abstract

Spinal cord injury (SCI) is a serious central trauma, leading to severe dysfunction of motor and sensory systems. Secondary injuries, such as apoptosis and cell autophagy, significantly impact the motor function recovery process. Metformin is a widely used oral anti-diabetic agent for type 2 diabetes in the world. It has been demonstrated to promote autophagy and inhibit apoptosis in the nervous system. However, its role in recovery following SCI is still unknown. In this study, we determined that motor function, assessed using the Basso, Beattie, and Bresnahan (BBB) locomotor assessment scale, was significantly higher in rats treated with metformin following injury. Nissl staining revealed that metformin also increased the number of surviving neurons in the spinal cord lesion. Western blot and immunofluorescent analysis revealed that mammalian target of rapamycin (mTOR) and P70S6 kinase (P70S6K) decreased, while the expression of autophagy markers increased and apoptosis markers declined in animals treated with metformin following SCI. Taken together, these findings suggest that metformin functions as a neuroprotective agent following SCI by promoting autophagy and inhibiting apoptosis by regulating the mTOR/P70S6K signaling pathway.

Swimming Exercise Promotes Post-injury Axon Regeneration and Functional Restoration through AMPK

“…Tissue-specific rescue experiments suggested that AAK-2 acts both in neuron and muscle for enhanced axon regeneration and functional recovery. Few studies indicated that activation of AMPK by metformin has positive effect after spinal cord injury ( Zhang et al, 2017 ; Guo et al, 2018 ). Pharmacological activation of AMPK can promote muscle fiber regeneration in a mouse myopathy model ( Peralta et al, 2016 ).…”

Metformin Promotes the Survival of Random-Pattern Skin Flaps by Inducing Autophagy via the AMPK-mTOR-TFEB signaling pathway

“…MET is a common oral hypoglycemic agent used to treat type 2 diabetes and prevent vascular complications 15, 16. Recent studies examining the therapeutic effects of MET have demonstrated its efficacy in a wide range of conditions, including diabetic cardiomyopathy 17, acute hyperglycemia-chemical hypoxia 20, 21, and spinal cord injury 18. MET treatment has also been shown to improve flap survival in a random skin flap model 22; however, the mechanisms underlying these effects remain poorly understood.…”

Effect of metformin on human periodontal ligament stem cells cultured with polydopamine‐templated hydroxyapatite

“…The molecular mechanism by which metformin improves the biocompatibility of tHA remains unknown. Studies have demonstrated that metformin decreases cell apoptosis and cytotoxicity via regulating the AMPK and mTOR pathways . Studies also suggest that metformin reduces ROS levels through the AMPK–forkhead box O3 (FOXO3) pathway .…”