Oligoprotective Effect of Metformin Through the Ampk-Dependent on Restoration of Mitochondrial Hemostasis in the Cuprizone-Induced Multiple Sclerosis Model Publisher Pubmed



Largani SHH¹ ; Borhanihaghighi M¹ ; Pasbakhsh P¹ ; Mahabadi VP² ; Nekoonam S¹ ; Shiri E¹ ; Kashani IR¹ ; Zendehdel A³ Show Affiliations
Source: Journal of Molecular Histology Published:2019

Abstract

Oxidative stress with mitochondrial defects has a central role in the development and deterioration of Multiple sclerosis (MS). According to new findings of the effects of metformin on mitochondrial function, has attracted a lot of attention. Furthermore, it is suggested that metformin exerts its beneficial influence through AMP-activated protein kinase (AMPK) pathway. In the current study, we investigated the possible protective effects of metformin on oxidative stress and mitochondrial function by activating the AMPK pathway in the cuprizone-induced demyelination. Mice were fed with cuprizone for 6 weeks. Animals simultaneously received metformin. After sacrificing animals, myelinations, and gliosis, changes in transcription factor and biochemical analysis were assessed. Transmission electron microscopy and luxol fast blue staining revealed that the myelinated axons within corpus callosum of cuprizone-induced demyelination animals increased after administration of metformin. Metformin also upregulated the expression of mitochondrial biogenesis genes. Furthermore, the biochemical analysis demonstrated that metformin ameliorated the oxidative stress induced by cuprizone. Immunohistochemistry analysis showed that astrogliosis and microgliosis were decreased after metformin administration while it enhanced the number of oligodendrocytes. Our data implicated that metformin exerts its therapeutic effects on MS by AMPK signaling improved mitochondrial homeostasis and protected oligodendrocytes. © 2019, Springer Nature B.V.