title: Targeted ablation of oligodendrocytes triggers axonal damage.
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.
authors.affiliation: Max-Planck-Institute of Experimental Medicine, Göttingen, Germany.
authors.forename: Aniket
authors.initials: A
authors.lastname: Ghosh
authors.forename: Natalia
authors.initials: N
authors.lastname: Manrique-Hoyos
authors.forename: Aaron
authors.initials: A
authors.lastname: Voigt
authors.forename: Jörg B
authors.initials: JB
authors.lastname: Schulz
authors.forename: Mario
authors.initials: M
authors.lastname: Kreutzfeldt
authors.forename: Doron
authors.initials: D
authors.lastname: Merkler
authors.forename: Mikael
authors.initials: M
authors.lastname: Simons
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000187:drug effects / Q000473:pathology*; D004167:Diphtheria Toxin / Q000494:pharmacology; D004331:Drosophila melanogaster / Q000187:drug effects / Q000378:metabolism; D019426:Integrases / Q000378:metabolism; D008124:Locomotion / Q000187:drug effects; D008136:Longevity / Q000187:drug effects; D051379:Mice; D017628:Microglia / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D009836:Oligodendroglia / Q000187:drug effects / Q000473:pathology*
chemical_list: D004167:Diphtheria Toxin; C045073:Cre recombinase; D019426:Integrases