IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson's disease

C. Barcia, C. M. Ros, V. Annese, A. Gómez, F. Ros-Bernal, C. Aguado-Year, M. E. Martínez-Paǵn, V. De Pablos, E. Fernandez-Villalba, M. T. Herrero*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

140 Citations (Scopus)

Abstract

To through light on the mechanisms underlying the stimulation and persistence of glial cell activation in Parkinsonism, we investigate the function of IFN-γ and TNF-α in experimental models of Parkinson's disease and analyze their relation with local glial cell activation. It was found that IFN-γ and TNF-α 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-γR signaling in both microglial and astroglial cells. In addition, experiments performed in IFN-γ and TNF-α KO mice treated with MPTP revealed that, even before dopaminergic cell death can be observed, the presence of IFN-γ and TNF-α 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-γ signaling, together with the contribution of TNF-α, have a critical and cell-specific role in stimulating and maintaining glial cell activation in Parkinsonism.

Original languageEnglish
Article numbere142
JournalCell death and disease
Volume2
Issue number4
DOIs
Publication statusPublished - Apr 2011

Keywords

  • Glial cells
  • IFN-γ
  • Inflammation
  • Parkinson's disease
  • Pro-inflammatory cytokines
  • TNF-α

Fingerprint

Dive into the research topics of 'IFN-γ signaling, with the synergistic contribution of TNF-α, mediates cell specific microglial and astroglial activation in experimental models of Parkinson's disease'. Together they form a unique fingerprint.

Cite this