Therapeutic Effect of the Mitochondria-Targeted Antioxidant SkQ1 on the Culture Model of Multiple Sclerosis.

Elena K Fetisova,Konstantin G Lyamzaev,Maria S Muntyan,Boris V Chernyak

doi:10.1155/2019/2082561

Elena K Fetisova, Konstantin G Lyamzaev + Show 2 more

Open Access

https://doi.org/10.1155/2019/2082561

Copy DOI

Abstract

Multiple sclerosis (MS) is a heterogeneous autoimmune disease of unknown etiology characterized by inflammation, demyelination, and axonal degeneration that affects both the white and gray matter of CNS. Recent large-scale epidemiological and genomic studies identified several genetic and environmental risk factors for the disease. Among them are environmental factors of infectious origin, possibly causing MS, which include Epstein-Barr virus infection, reactivation of some endogenous retrovirus groups, and infection by pathogenic bacteria (mycobacteria, Chlamydia pneumoniae, and Helicobacter pylori). However, the nature of the events leading to the activation of immune cells in MS is mostly unknown and there is no effective therapy against the disease. Amazingly, whatever the cause of the disease, signs of damage to the nerve tissue with MS lesions were the same as with infectious leprosy, while in the latter case nitrozooxidative stress was suggested as the main cause of the nerve damage. With this in mind and following the hypothesis that excessive production of mitochondrial reactive oxygen species critically contributes to MS pathogenesis, we studied the effect of mitochondria-targeted antioxidant SkQ1 in an in vitro MS model of the primary oligodendrocyte culture of the cerebellum, challenged with lipopolysaccharide (LPS). SkQ1 was found to accumulate in the mitochondria of oligodendrocytes and microglial cells, and it was also found to prevent LPS-induced inhibition of myelin production in oligodendrocytes. The results implicate that mitochondria-targeted antioxidants could be promising candidates as components of a combined therapy for MS and related neurological disorders.

Highlights

Typical multiple sclerosis (MS) is a widespread chronic inflammatory demyelinating disease of the central nervous system (CNS), a hallmark of which is considered the demyelination of cerebral white matter and a consequent progressive neuronal loss and neurological disability
Oligodendroglia is the first to emigrate from the explant due to the mobility of oligodendrocytes and the ability of cells to change their shape and size, which was well documented by several authors [18, 25, 26]
All the cell types that inhabit the coverslip can exchange metabolites among themselves. This means that oxidative stress factors are common to all cells of each coverslip, each of which, in general, contains a total set of neuroglial cells represented in the cerebellum: neurons, astrocytes, oligodendrocytes, and microglia

Summary

Introduction

Typical multiple sclerosis (MS) is a widespread chronic inflammatory demyelinating disease of the central nervous system (CNS), a hallmark of which is considered the demyelination of cerebral white matter and a consequent progressive neuronal loss and neurological disability. The recent observation of the sharp appearance of the free mitochondrial DNA in the serum of patients with MS at the onset of the disease supports this view [3]. In this context, it should be noted that myelin-producing glial cells called oligodendrocytes are susceptible to oxidative stress and inflammatory mediators [4,5,6] and are one of the main targets of MS. Application of MitoQ to experimental autoimmune encephalomyelitis (EAE), a mouse model of MS, demonstrated an increase

Methods

Results

Conclusion