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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
9
|
| pubmed:dateCreated |
1998-11-18
|
| pubmed:abstractText |
Type I IFNs, which include IFN-alpha, appear to have complex and broad-ranging actions in the central nervous system (CNS) that may result in protection or injury. To better understand these issues, we generated transgenic mice that produce IFN-alpha1 chronically from astrocytes. These glial fibrillary acidic protein-IFN-alpha transgenic mice developed a progressive inflammatory encephalopathy, with marked calcium mineralization, meninoencephalitis, gliosis, and neurodegeneration. Many features of this murine encephalopathy resembled those found in certain human encephalopathies of unknown etiology; these diseases, exemplified by Aicardi-Goutières syndrome and some viral encephalopathies, show increased intrathecal production of IFN-alpha. Our data suggest that IFN-alpha overproduction may be the primary factor initiating these human diseases. Following intracerebral infection with lymphocytic choriomeningitis virus, glial fibrillary acidic protein-IFN-alpha mice had significantly increased survival rates associated with markedly reduced virus titers and immune pathology in the brain but normal peripheral CTL responses. Therefore, the production of IFN-alpha in the CNS can be a two-edged sword that on the one hand confers protection against a lethal viral infection but on the other causes significant injury to the brain. These transgenic mice provide a novel animal model in which to further evaluate the mechanisms that underlie the diverse actions of type I IFNs in the intact CNS.
|
| pubmed:grant | |
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Glial Fibrillary Acidic Protein,
http://linkedlifedata.com/resource/pubmed/chemical/Interferon-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Tissue Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Nov
|
| pubmed:issn |
0022-1767
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
1
|
| pubmed:volume |
161
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
5016-26
|
| pubmed:dateRevised |
2007-11-14
|
| pubmed:meshHeading |
pubmed-meshheading:9794439-Animals,
pubmed-meshheading:9794439-Astrocytes,
pubmed-meshheading:9794439-B-Lymphocytes,
pubmed-meshheading:9794439-CD4-Positive T-Lymphocytes,
pubmed-meshheading:9794439-Calcinosis,
pubmed-meshheading:9794439-Gene Expression Regulation,
pubmed-meshheading:9794439-Glial Fibrillary Acidic Protein,
pubmed-meshheading:9794439-Gliosis,
pubmed-meshheading:9794439-Interferon-alpha,
pubmed-meshheading:9794439-Lymphocytic Choriomeningitis,
pubmed-meshheading:9794439-Meningoencephalitis,
pubmed-meshheading:9794439-Mice,
pubmed-meshheading:9794439-Mice, Transgenic,
pubmed-meshheading:9794439-Nerve Tissue Proteins,
pubmed-meshheading:9794439-Neurodegenerative Diseases,
pubmed-meshheading:9794439-Recombinant Fusion Proteins,
pubmed-meshheading:9794439-T-Lymphocytes, Cytotoxic,
pubmed-meshheading:9794439-Transgenes,
pubmed-meshheading:9794439-Viral Load
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Transgenic expression of IFN-alpha in the central nervous system of mice protects against lethal neurotropic viral infection but induces inflammation and neurodegeneration.
|
| pubmed:affiliation |
Department of Neuropharmacology, The Scripps Research Institute, La Jolla, CA 92037, USA.
|
| pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
|