ORIGINAL ARTICLE Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation Nima Sanadgol 1 & Fereshteh Golab 2 & Hassan Askari 3 & Fatemeh Moradi 4 & Marziyeh Ajdary 2 & Mehdi Mehdizadeh 5 Received: 26 May 2017 /Accepted: 21 August 2017 # Springer Science+Business Media, LLC 2017 Abstract Multiple Sclerosis (MS), is a disease that degener- ates myelin in central nervous system (CNS). Reactive oxygen species (ROSs) are toxic metabolites, and accumulating data indicate that ROSs-mediated apoptosis of oligodendrocytes (OLGs) plays a major role in the pathogenesis of MS under oxidative stress conditions. In this study, we investigated the role of endogenous antioxidant alpha-lipoic acid (ALA) as ROSs scavenger in the OLGs loss and myelin degeneration during cuprizone (cup)-induced demyelination in the experi- mental model of MS. Our results have shown that ALA treat- ment significantly increased population of mature OLGs (MOG + cells), as well as decreased oxidative stress (ROSs, COX-2 and PGE2) and apoptosis mediators (caspase-3 and Bax/Bcl2 ratio) in corpus callosum (CC). Surprisingly, ALA significantly stimulates population of NG2 chondroitin sulfate proteoglycan positive glia (NG2 + cells or polydendrocytes), from week 4 afterward. Accordingly ALA could prevents apo- ptosis, delays demyelination and recruits OLGs survival and regeneration mechanisms in CC. We conclude that ALA has protective effects against toxic demyelination via reduction of redox signaling, and alleviation of polydendrocytes vulnerabil- ity to excitotoxic challenge. Keywords ALA . Cuprizone . Demyelination . Multiple sclerosis . ROS Abbreviations ALA Alpha-lipoic acid CC Corpus callosum CNS Central nervous system COX-1 Cyclooxygenase-1 COX-2 Cyclooxygenase-2 MS Multiple Sclerosis MOG Myelin oligodendrocyte glycoprotein OLGs Oligodendrocytes OPCs Oligodendrocyte precursor cells PGE2 Prostaglandin E2 ROSs Reactive oxygen species RNSs Reactive nitrogen species Introduction Multiple sclerosis (MS) is a disease of the central nervous system (CNS) in which the immune system mistakenly attacks the cells that produce myelin sheath. During diseases expan- sion, myelin becomes inflamed and swollen, gets detached from neuronal fibers and ultimately removed by immune cells (Ramroodi et al. 2013). Following the myelin damage, patches of rigid scar tissues (sclerosis) develop on nerve fibers which divert or slow down the speed of nerve impulses. Eventually, this process leads to inability of axons in transmit- ting nerve messages, or increase in the energy needed by neu- rons to transmit a message (Mirshafiey & Mohsenzadegan, * Mehdi Mehdizadeh mehdizadeh.m@iums.ac.ir 1 Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran 2 Cellular and Molecular Research Center, Iran University of Medical Science, P.O. Box 14665-354, Tehran, Iran 3 Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran 4 Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran 5 Cellular and Molecular Research Center, Faculty of Advanced Technologies in Medicine, Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran Metab Brain Dis DOI 10.1007/s11011-017-0099-9