Article abstract
Nature Genetics 39, 969 - 976 (2007)
Published online: 22 July 2007 | doi:10.1038/ng2070
Axonal loss and neuroinflammation caused by peroxisome-deficient oligodendrocytes
Celia M Kassmann1, Corinna Lappe-Siefke1, Myriam Baes2, Britta Brügger3, Alexander Mildner4, Hauke B Werner1, Oliver Natt5, Thomas Michaelis5, Marco Prinz4, Jens Frahm5 & Klaus-Armin Nave1
Abstract
Oligodendrocytes myelinate axons for rapid impulse conduction and contribute to normal axonal functions in the central nervous system. In multiple sclerosis, demyelination is caused by autoimmune attacks, but the role of oligodendroglial cells in disease progression and axon degeneration is unclear. Here we show that oligodendrocytes harbor peroxisomes whose function is essential for maintaining white matter tracts throughout adult life. By selectively inactivating the import factor PEX5 in myelinating glia, we generated mutant mice that developed normally, but within several months showed ataxia, tremor and premature death. Absence of functional peroxisomes from oligodendrocytes caused widespread axonal degeneration and progressive subcortical demyelination, but did not interfere with glial survival. Moreover, it caused a strong proinflammatory milieu and, unexpectedly, the infiltration of B and activated CD8+ T cells into brain lesions. We conclude that peroxisomes provide oligodendrocytes with an essential neuroprotective function against axon degeneration and neuroinflammation, which is relevant for human demyelinating diseases.
- Department of Neurogenetics, Max Planck Institute of Experimental Medicine, Hermann-Rein-Strasse 3, D-37075 Göttingen, Germany.
- Laboratory for Cell Metabolism, Faculty of Pharmacy, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
- Biochemie-Zentrum, Universität Heidelberg, D-69120 Heidelberg, Germany.
- Department of Neuropathology, University of Göttingen, D-37075 Göttingen, Germany.
- Biomedizinische NMR Forschungs GmbH am Max-Planck-Institut für biophysikalische Chemie, 37077 Göttingen, Germany.
Correspondence to: Klaus-Armin Nave1 e-mail: nave@em.mpg.de
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