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pubmed-article:11002285pubmed:abstractTextFocal demyelination models provide powerful tools to study demyelination and remyelination in the central nervous system. In this report, we present a novel technique, which selectively targets oligodendrocytes within the spinal cord of transgenic mice to produce focal demyelination. Transgenic mice expressing the E. coli LacZ (beta-galactosidase) gene from the myelin basic protein promotor allowed for oligodendrocyte-specific cleavage of topically applied fluorescein-di-beta-galactopyranoside liberating photoactivatable fluorescein. Subsequent fluorescence illumination generated oxygen radicals that oxidized a second exogenous substrate, 3-amino-9-ethyl carbazole, to form a toxic precipitate within oligodendrocytes. Histochemical staining of the spinal cord dorsal columns 8 days following phototargeting revealed that the treated region no longer contained beta-galactosidase-positive cells. Focal demyelination of the dorsal columns was observed to a depth of 150 microm in transverse semithin plastic sections. Numerous bundles of naked axons interspersed with myelin, debris-laden macrophages, and reactive astrocytes were evident by electron microscopy. Remyelination of axons by both oligodendrocytes and invading Schwann cells was observed within the treated region 14 days after phototargeting. Newly generated oligodendrocytes were identified within the demyelinated region by their incorporation of bromodeoxyuridine. Thus, this novel focal demyelination protocol provides: (1) a method for selective targeted ablation of oligodendrocytes in vivo, (2) control over the extent of the demyelinated region, with (3) an environment that maintains its remyelination capacity. Phototargeted ablation of oligodendrocytes may therefore be a useful model for studying axon-glia interactions, axon regeneration within a demyelinated zone, and remyelination of axons.lld:pubmed
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pubmed-article:11002285pubmed:authorpubmed-author:PetersonA CAClld:pubmed
pubmed-article:11002285pubmed:authorpubmed-author:BourqueJ AJAlld:pubmed
pubmed-article:11002285pubmed:authorpubmed-author:VanderluitJ...lld:pubmed
pubmed-article:11002285pubmed:copyrightInfoCopyright 2000 Wiley-Liss, Inc.lld:pubmed
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pubmed-article:11002285pubmed:volume62lld:pubmed
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pubmed-article:11002285pubmed:pagination28-39lld:pubmed
pubmed-article:11002285pubmed:dateRevised2008-11-21lld:pubmed
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pubmed-article:11002285pubmed:articleTitleModel for focal demyelination of the spinal dorsal columns of transgenic MBP-LacZ mice by phototargeted ablation of oligodendrocytes.lld:pubmed
pubmed-article:11002285pubmed:affiliationCORD (Collaboration on Repair Discoveries), Vancouver, British Columbia, Canada.lld:pubmed
pubmed-article:11002285pubmed:publicationTypeJournal Articlelld:pubmed
pubmed-article:11002285pubmed:publicationTypeResearch Support, Non-U.S. Gov'tlld:pubmed