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          Institute: MPI für Neurobiologie     Collection: Emeriti     Display Documents

ID: 27071.0, MPI für Neurobiologie / Emeriti
Cytotoxic potential of proinflammatory cytokines: combined deletion of TNF receptors TNFR1 and TNFR2 prevents motoneuron cell death after facial axotomy in adult mouse
Authors:Raivich, G.; Liu, Z. Q.; Kloss, C. U. A.; Labow, M.; Bluethmann, H.; Bohatschek, M.
Date of Publication (YYYY-MM-DD):2002-12
Title of Journal:Experimental Neurology
Journal Abbrev.:Exp. Neurol.
Issue / Number:2
Start Page:186
End Page:193
Review Status:Peer-review
Audience:Not Specified
Abstract / Description:Neural injury is known to trigger inflammatory changes, including the synthesis of proinflammatory cytokines such as interleukin-1-beta (IL1beta), tumor necrosis factor-alpha (TNFalpha), and interferon-gamma (IFNgamma) [G. Raivich, L. L. Jones, C. U. A. Kloss, A. Werner, H. Neumann, and G. W. Kreutzberg, 1998, J Neurosci, 18: 5804 -5816] that may play a pivotal role in mediating the cellular response in the affected brain tissue. Here we examined the effects of transgenic deletion of receptors for these cytokines on neuronal cell loss in the adult mouse facial motor nucleus after a peripheral, facial nerve cut. Homozygous deletion of IL1 receptor 1 (ILIRl), TNF receptor 1 or 2 (TNFR1 or TNFR2), or IFNgamma receptor 1 (IFNgammaR1) alone had no effect but combined deletion of TNFR1 and TNFR2 caused a striking absence of alphaX beta2 integrin/IBA1-double-labeled, phagocytic microglial nodules in the axotomized facial motor nucleus 14 days after nerve cut. Moreover, this combined deletion also led to an almost complete prevention of cell loss by Day 29. Additional neuronal cell counts at Day 60 revealed a second phase of motoneuron cell disappearance, which did not depend on the presence of TNF receptors. However, there was still the same 22% difference in the total number of motoneurons between the wild-type and TNFR1 & 2-deficient mice, underlining the role of TNF ligands and both TNF receptors in mediating the early phase of neuronal cell loss after traumatic injury. (C) 2002 Elsevier Science (USA).
Free Keywords:motoneuron; microglia; phagocytosis; cell death; alphaX beta2; CD11c/CD18 integrin; cytokine receptor
External Publication Status:published
Document Type:Article
Affiliations:MPI für Neurobiologie/Emeriti /Neuromorphology (Kreutzberg)
External Affiliations:Univ Coll London, Dept Anat, Dept Obstet & Gynaecol, Perinatal; Brain Repair Grp, 86-96 Chenies Mews, London WC1E 6HX, England; Univ Coll London, Dept Anat, Dept Obstet & Gynaecol, Perinatal Brain Repair Grp, London WC1E 6HX, England; F Hoffmann La Roche & Co Ltd, CH-4002 Basel, Switzerland; Hoffmann La Roche Inc, Nutley, NJ 07110 USA
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