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Title

Targeted ablation of oligodendrocytes triggers axonal damage

Authors
Ghosh, Aniket
Manrique-Hoyos, Natalia
Voigt, Aaron
Schulz, Jörg B
Simons, Mikael
Published in PLOS ONE. 2011, vol. 6, no. 7, p. e22735
Abstract Glial dysfunction has been implicated in a number of neurodegenerative diseases. In this study we investigated the consequences of glial and oligodendrocyte ablation on neuronal integrity and survival in Drosophila and adult mice, respectively. Targeted genetic ablation of glia was achieved in the adult Drosophila nervous system using the GAL80-GAL4 system. In mice, oligodendrocytes were depleted by the injection of diphtheria toxin in MOGi-Cre/iDTR double transgenic animals. Acute depletion of oligodendrocytes induced axonal injury, but did not cause neuronal cell death in mice. Ablation of glia in adult flies triggered neuronal apoptosis and resulted in a marked reduction in motor performance and lifespan. Our study shows that the targeted depletion of glia triggers secondary neurotoxicity and underscores the central contribution of glia to neuronal homeostasis. The models used in this study provide valuable systems for the investigation of therapeutic strategies to prevent axonal or neuronal damage.
Keywords AnimalsAstrocytes/drug effects/metabolism/pathologyAxons/drug effects/pathologyDiphtheria Toxin/pharmacologyDrosophila melanogaster/drug effects/metabolismIntegrases/metabolismLocomotion/drug effectsLongevity/drug effectsMiceMicroglia/drug effects/metabolism/pathologyOligodendroglia/drug effects/pathology
Identifiers
PMID: 21818378
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Article (Published version) (7.9 MB) - public document Free access
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Research group La Sclérose en plaques (908)
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GHOSH, Aniket et al. Targeted ablation of oligodendrocytes triggers axonal damage. In: PLOS ONE, 2011, vol. 6, n° 7, p. e22735. https://archive-ouverte.unige.ch/unige:24273

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Deposited on : 2012-11-30

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