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          Institute: MPI für experimentelle Medizin     Collection: Neurogenetics     Display Documents



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ID: 19817.0, MPI für experimentelle Medizin / Neurogenetics
Patients lacking the major CNS myelin protein, proteolipid protein 1, develop length-dependent axonal degeneration in the absence of demyelination and inflammation
Authors:Garbern, J. Y.; Yool, D. A.; Moore, G. J.; Wilds, I. B.; Faulk, M. W.; Klugmann, M.; Nave, Klaus-Armin; Sistermans, E. A.; van der Knaap, M. S.; Bird, T. D.; Shy, M. E.; Kamholz, J. A.; Griffiths, I. R.
Language:English
Date of Publication (YYYY-MM-DD):2002-03
Title of Journal:Brain
Journal Abbrev.:Brain
Volume:125
Start Page:551
End Page:561
Review Status:Peer-review
Audience:Experts Only
Abstract / Description:Axonal degeneration contributes to clinical disability in the acquired demyelinating disease multiple sclerosis. Axonal degeneration occurs during acute attacks, associated with inflammation, and during the chronic progressive phase of the disease in which inflammation is not prominent. To explore the importance of interactions between oligodendrocytes and axons in the CNS, we analysed the brains of rodents and humans with a null mutation in the gene encoding the major CNS myelin protein, proteolipid protein (PLP1, previously PLP). Histological analyses of the CNS of Plp1 null mice and of autopsy material from patients with null PLP1 mutations were performed to evaluate axonal and myelin integrity. In vivo proton magnetic resonance spectroscopy (MRS) of PLP1 null patients was conducted to measure levels of N-acetyl aspartate (NAA), a marker of axonal integrity. Length-dependent axonal degeneration without demyelination was identified in the CNS of Plp1 null mice. Proton MRS of PLP1-deficient patients showed reduced NAA levels, consistent with axonal loss. Analysis of patients' brain tissue also demonstrated a length-dependent pattern of axonal loss without significant demyelination. Therefore, axonal degeneration occurs in humans as well as mice lacking the major myelin protein PLP1. This degeneration is length-dependent, similar to that found in the PNS of patients with the inherited demyelinating neuropathy, CMT1A, but is not associated with significant demyelination. Disruption of PLP1- mediated axonal-glial interactions thus probably causes this axonal degeneration. A similar mechanism may be responsible for axonal degeneration and clinical disability that occur in patients with multiple sclerosis.
Free Keywords:Pelizaeus-Merzbacher disease; axonal; proteolipid protein 1; DM20; N-acetyl aspartate; magnetic resonance spectroscopy
Comment of the Author/Creator:Date: 2002, MAR
External Publication Status:published
Document Type:Article
Communicated by:Klaus-Armin Nave
Affiliations:MPI für experimentelle Medizin/Neurogenetics
External Affiliations:Wayne State Univ, Sch Med, Dept Neurol, 421E Canfield Room; 3206, Detroit, MI 48201 USA; Wayne State Univ, Sch Med, Dept Neurol, Detroit, MI 48201 USA; Wayne State Univ, Sch Med, Ctr Mol Med & Genet, Detroit, MI 48201 USA; Wayne State Univ, Sch Med, Dept Psychiat & Behav Sci, Detroit, MI USA; Univ Washington, Dept Neurol, Seattle, WA 98195 USA; Seattle Vet Adm Med Ctr, Seattle, WA USA; Univ Med Ctr Nijmegen, Dept Human Genet, Nijmegen, Netherlands; Free Univ Amsterdam, Med Ctr, Amsterdam, Netherlands; Univ Glasgow, Dept Vet Clin Studies, Appl Neurobiol Grp, Glasgow, Lanark, Scotland
Identifiers:ISI:000174361700011 [ID No:1]
ISSN:0006-8950 [ID No:2]
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