Toggle Main Menu Toggle Search

Open Access padlockePrints

Chronic glial activation, neurodegeneration, and APP immunoreactive deposits following acute administration of double-stranded RNA

Lookup NU author(s): Alexander Keith, Dr Sue Davis, Arthur Oakley, Professor Jim Edwardson, Dr Christopher Morris


Full text for this publication is not currently held within this repository. Alternative links are provided below where available.


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.

Publication metadata

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


DOI: 10.1002/glia.10276

PubMed id: 12951652


Altmetrics provided by Altmetric