title: Dynamics of oligodendrocyte responses to anterograde axonal (Wallerian) and terminal degeneration in normal and TNF-transgenic mice.
abstract: The inflammatory cytokine tumour necrosis factor (TNF) can both induce oligodendrocyte and myelin pathology and promote proliferation of oligodendrocyte progenitor cells and remyelination. We have compared the response of the oligodendrocyte lineage to anterograde axonal (Wallerian) and terminal degeneration and lesion-induced axonal sprouting in the hippocampal dentate gyrus in TNF-transgenic mice with the response in genetically normal mice. Transectioning of the entorhino-dentate perforant path axonal projection increased hippocampal TNF mRNA expression in both types of mice, but to significantly larger levels in the TNF-transgenics. At 5 days after axonal transection, numbers of oligodendrocytes and myelin basic protein (MBP) mRNA expression in the denervated dentate gyrus in TNF-transgenic mice had increased to the same extent as in nontransgenic littermates. At this time, transgenics showed a tendency towards a greater increase in the number of juxtaposed, potentially proliferating oligodendrocytes. Noteworthy, at day 5 we also observed upregulation of MBP mRNA expression in adjacent hippocampal subregions with lesion-induced axonal sprouting, which were devoid of axonal degeneration, raising the possibility that sprouting axons provide trophic stimuli to the oligodendrocyte lineage. Twenty-eight days after lesioning, oligodendrocyte numbers and MBP mRNA expression were reduced to near normal levels. However, oligodendrocyte densities in the TNF-transgenic mice were significantly lower than in nontransgenics. We conclude that the early response of the oligodendrocyte lineage to axonal lesioning and lesion-induced axonal sprouting appears unaffected by the supranormal TNF levels in the TNF-transgenic mice. TNF may, however, have long-term inhibitory effects on the oligodendrocyte response to axonal lesioning.
authors.affiliation: Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark-Odense, Odense C, Denmark.|Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Nina
authors.initials: N
authors.lastname: Drøjdahl
authors.affiliation: Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark-Odense, Odense C, Denmark.
authors.forename: Christina
authors.initials: C
authors.lastname: Fenger
authors.affiliation: Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark-Odense, Odense C, Denmark.
authors.forename: Helle H
authors.initials: HH
authors.lastname: Nielsen
authors.affiliation: Montreal Neurological Institute, McGill University, Montreal, Quebec, Canada.
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
authors.affiliation: Anatomy and Neurobiology, Institute of Medical Biology, University of Southern Denmark-Odense, Odense C, Denmark.
authors.forename: Bente
authors.initials: B
authors.lastname: Finsen
mesh_terms: D000818:Animals; D001369:Axons / Q000378:metabolism / Q000473:pathology; D019771:Axotomy; D002455:Cell Division / Q000235:genetics; D006624:Hippocampus / Q000166:cytology / Q000254:growth & development / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D004676:Myelin Basic Protein / Q000378:metabolism; D009413:Nerve Fibers, Myelinated / Q000378:metabolism / Q000473:pathology; D009414:Nerve Growth Factors / Q000378:metabolism; D009416:Nerve Regeneration / Q000235:genetics*; D009473:Neuronal Plasticity / Q000235:genetics*; D009836:Oligodendroglia / Q000166:cytology / Q000378:metabolism*; D019580:Perforant Pathway / Q000293:injuries / Q000503:physiopathology / Q000601:surgery; D012333:RNA, Messenger / Q000378:metabolism; D011930:Reaction Time / Q000502:physiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*; D015854:Up-Regulation / Q000235:genetics; D014855:Wallerian Degeneration / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology
chemical_list: D004676:Myelin Basic Protein; D009414:Nerve Growth Factors; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha