Oligodendrocyte Plasticity with an Intact Cell Body In Vitro

Manabu Makinodan,Michihiro Toritsuka,Daisuke Ikawa,Aya Okuda-Yamamoto,Hiroaki Okuda,Toshifumi Kishimoto,Kouko Tatsumi,Akio Wanaka,Sohei Kimoto,Yu Nakamura,Tomohiko Takeda,Fernando De Castro

doi:10.1371/journal.pone.0066124

Manabu Makinodan, Michihiro Toritsuka + Show 10 more

Open Access

https://doi.org/10.1371/journal.pone.0066124

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Journal: PloS one	Publication Date: Jun 7, 2013
Citations: 27	License type: CC BY 4.0

Affiliation: Nara Medical University, Kagawa University

Abstract

Demyelination is generally regarded as a consequence of oligodendrocytic cell death. Oligodendrocyte processes that form myelin sheaths may, however, degenerate and regenerate independently of the cell body, in which case cell death does not necessarily occur. We provide here the first evidence of retraction and regeneration of oligodendrocyte processes with no cell death in vitro, using time-lapse imaging. When processes were severed mechanically in vitro, the cells did not undergo cell death and the processes regenerated in 36 h. In a separate experiment, moderate N-methyl-D-aspartate (NMDA) stimuli caused process retraction without apparent cell death, and the processes regained their elaborate morphology after NMDA was removed from the culture medium. These results strongly suggest that demyelination and remyelination can take place without concomitant cell death, at least in vitro. Process regeneration may therefore become a target for future therapy of demyelinating disorders.

Highlights

In the active lesions of demyelinating disorders such as multiple sclerosis, oligodendrocytes are thought to undergo cell death [1,2,3]
It is generally accepted that the regenerating oligodendrocytes derive from oligodendrocyte precursor cells (OPCs), which are widespread in the central nervous system [4], [5]
NMDA (Sigma) in Hank’s balanced salt solution (HBSS) or the equivalent volume of HBSS was added to the medium, to a final concentration of 5 mM, for the retraction of oligodendrocyte processes

Summary

Introduction

In the active lesions of demyelinating disorders such as multiple sclerosis, oligodendrocytes are thought to undergo cell death [1,2,3]. It is generally accepted that the regenerating oligodendrocytes derive from oligodendrocyte precursor cells (OPCs), which are widespread in the central nervous system [4], [5]. Demyelination and remyelination could reflect the processes being degenerated and regenerated, respectively, in which case whole cells would not have to turn over. In line with this speculation, differential distribution and function of glutamatergic receptors have been reported: AMPA (a-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid)/ kainite receptor subunits are mainly expressed in the soma, whereas NMDA (N-methyl-D-aspartate) receptor subunits are found predominantly in the processes of oligodendrocytes [9]. Nonlethal oxidative stress leads to a rapid and reversible shortening of oligodendrocyte processes which is prevented by antioxidants [11]

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