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Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation

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Abstract

Multiple Sclerosis (MS), is a disease that degenerates 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 experimental model of MS. Our results have shown that ALA treatment 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 apoptosis, 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 vulnerability to excitotoxic challenge.

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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

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Authors and Affiliations

  1. Department of Biology, Faculty of Sciences, University of Zabol, Zabol, Iran

    Nima Sanadgol

  2. Cellular and Molecular Research Center, Iran University of Medical Science, P.O. Box 14665-354, Tehran, Iran

    Fereshteh Golab & Marziyeh Ajdary

  3. Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, Tehran, Iran

    Hassan Askari

  4. Department of Anatomy, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Fatemeh Moradi

  5. Cellular and Molecular Research Center, Faculty of Advanced Technologies in Medicine, Department of Anatomy, Iran University of Medical Sciences, Tehran, Iran

    Mehdi Mehdizadeh

Authors
  1. Nima Sanadgol
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  2. Fereshteh Golab
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  3. Hassan Askari
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  4. Fatemeh Moradi
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  5. Marziyeh Ajdary
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  6. Mehdi Mehdizadeh
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Corresponding author

Correspondence to Mehdi Mehdizadeh.

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The authors declare that there are no conflicts of interest.

Funding

This work was supported by the Iran university medical science, grant number 81273037.

Contributors

Mehdi Mehdizadeh designed the study and collected funds. Nima Sanadgol performed the experiments and collected the data. Fatemeh Moradi did the statistical analysis and data interpretation, and finally marziyeh ajdary and nima sanadgol prepared the manuscript and literature search.

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Sanadgol, N., Golab, F., Askari, H. et al. Alpha-lipoic acid mitigates toxic-induced demyelination in the corpus callosum by lessening of oxidative stress and stimulation of polydendrocytes proliferation. Metab Brain Dis 33, 27–37 (2018). https://doi.org/10.1007/s11011-017-0099-9

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  • DOI: https://doi.org/10.1007/s11011-017-0099-9

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