IFN-c signaling, with the synergistic contribution of TNF-a, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s disease
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Other documents of the author: Barcia, Carlos; Ros Gómez, Carmen María; Annese, Valentina; Gómez, Aurora; Ros Bernal, Francisco; Aguado Yera, D.; Martínez Pagán, M. E.; De Pablos, Vicente; Fernández Villalba, Emiliano; Herrero Ezquerro, María Trinidad
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Title
IFN-c signaling, with the synergistic contribution of TNF-a, mediates cell specific microglial and astroglial activation in experimental models of Parkinson’s diseaseAuthor (s)
Date
2011Publisher
Nature Publishing GroupISSN
2041-4889Bibliographic citation
Citation: Cell Death and Disease (2011) 2, e142; doi:10.1038/cddis.2011.17Type
info:eu-repo/semantics/articlePublisher version
http://www.nature.com/cddis/journal/v2/n4/abs/cddis201117a.htmlVersion
info:eu-repo/semantics/publishedVersionSubject
Abstract
To through light on the mechanisms underlying the stimulation and persistence of glial cell activation in Parkinsonism, we
investigate the function of IFN-c and TNF-a in experimental models of Parkinson’s disease ... [+]
To through light on the mechanisms underlying the stimulation and persistence of glial cell activation in Parkinsonism, we
investigate the function of IFN-c and TNF-a in experimental models of Parkinson’s disease and analyze their relation with local
glial cell activation. It was found that IFN-c and TNF-a remained higher over the years in the serum and CNS of chronic
Parkinsonian macaques than in untreated animals, accompanied by sustained glial activation (microglia and astroglia) in the
substantia nigra pars compacta. Importantly, Parkinsonian monkeys showed persistent and increasing levels of IFN-cR signaling
in both microglial and astroglial cells. In addition, experiments performed in IFN-c and TNF-a KO mice treated with MPTP
revealed that, even before dopaminergic cell death can be observed, the presence of IFN-c and TNF-a is crucial for microglial and
astroglial activation, and, together, they have an important synergistic role. Both cytokines were necessary for the full level of
activation to be attained in both microglial and astroglial cells. These results demonstrate that IFN-c signaling, together with the
contribution of TNF-a, have a critical and cell-specific role in stimulating and maintaining glial cell activation in Parkinsonism. [-]
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Citation: Cell Death and Disease, 2011, Vol. 2, Num. 142Rights
Copyright 2011 Macmillan Publishers Limited All rights reserved 2041-4889/11
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