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Lookup NU author(s): Alexander Keith, Dr Sue Davis, Arthur Oakley, Professor Jim Edwardson, Dr Christopher Morris
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Several neurodegenerative disorders, including Alzheimer's and Parkinson's diseases, are associated with immunocompetent microglia, leading to the suggestion that chronic glial-mediated inflammation contributes to the neurodegeneration seen in these diseases. Little direct evidence supports this hypothesis, and no suitable rodent models exist that do not involve the use of blunt trauma or ischaemia, events that are infrequently encountered in the human disease state. In the present study, we report that administration of double-stranded RNA, a classical inducer of interferon-γ (IFN-γ), causes rapid and persistent activation of microglia and astrocytes, as well as induction of interleukin-1β (IL-β) and nitric oxide synthase. In close temporal succession to glial activation, there is neurodegeneration, with neuron loss involving apoptosis in selected brain regions including the septal nucleus, hippocampus, cortex and thalamus, along with hippocampal atrophy. This neuronal loss is accompanied by punctate deposits of material that are immunoreactive for amyloid precursor protein, β-amyloid peptide (Aβ), and apolipoprotein E. The findings may have clinical relevance, since the administration of the nonsteroidal antiinflammatory agent (NSAID) ibuprofen markedly reduces the neurodegeneration observed in the absence of significant glial inhibition. These findings may be relevant to the pathogenesis of Alzheimer's disease in particular, and to other neurodegenerative diseases involving inflammation. © 2003 Wiley-Liss, Inc.
Author(s): Melton LM, Keith AB, Davis S, Oakley AE, Edwardson JA, Morris CM
Publication type: Article
Publication status: Published
Journal: GLIA
Year: 2003
Volume: 44
Issue: 1
Pages: 1-12
ISSN (print): 0894-1491
ISSN (electronic): 1098-1136
Publisher: Wiley-Blackwell Publishing
URL: http://dx.doi.org/10.1002/glia.10276
DOI: 10.1002/glia.10276
PubMed id: 12951652
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