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Injury and Differentiation Following Inhibition of Mitochondrial Respiratory Chain Complex IV in Rat Oligodendrocytes

Lookup NU author(s): Dr Iryna Ziabreva, Graham Campbell, Jessica Zambonin, Dr Joanna Rorbach, Dr Mateusz Wydro, Dr Don Mahad

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Abstract

Oligodendrocyte lineage cells are susceptible to a variety of insults including hypoxia, excitotoxicity, and reactive oxygen species. Demyelination is a well-recognized feature of several CNS disorders including multiple sclerosis, white matter strokes, progressive multifocal leukoencephalopathy, and disorders due to mitochondrial DNA mutations. Although mitochondria have been implicated in the demise of oligodendrocyte lineage cells, the consequences of mitochondrial respiratory chain defects have not been examined. We determine the in vitro impact of established inhibitors of mitochondrial respiratory chain complex IV or cytochrome c oxidase on oligodendrocyte progenitor cells (OPCs) and mature oligodendrocytes as well as on differentiation capacity of OPCs from P0 rat. Injury to mature oligodendrocytes following complex IV inhibition was significantly greater than to OPCs, judged by cell detachment and mitochondrial membrane potential (MMP) changes, although viability of cells that remained attached was not compromised. Active mitochondria were abundant in processes of differentiated oligodendrocytes and MMP was significantly greater in differentiated oligodendrocytes than OPCs. MMP dissipated following complex IV inhibition in oligodendrocytes. Furthermore, complex IV inhibition impaired process formation within oligodendrocyte lineage cells. Injury to and impaired process formation of oligodendrocytes following complex IV inhibition has potentially important implications for the pathogenesis and repair of CNS myelin disorders. (C) 2010 Wiley-Liss, Inc.

Publication metadata

Author(s): Ziabreva I, Campbell G, Rist J, Zambonin J, Rorbach J, Wydro MM, Lassmann H, Franklin RJM, Mahad D

Publication type: Article

Publication status: Published

Journal: Glia

Year: 2010

Volume: 58

Issue: 15

Pages: 1827-1837

Print publication date: 01/11/2010

ISSN (print): 0894-1491

ISSN (electronic): 1098-1136

Publisher: John Wiley & Sons, Inc.

URL: http://dx.doi.org/10.1002/glia.21052

DOI: 10.1002/glia.21052

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