Abstract
In mammalians, toll-like receptors (TLR) signal-transduction pathways induce the expression of a variety of immune-response genes, including inflammatory cytokines. It is therefore plausible to assume that TLRs are mediators in glial cells triggering the release of cytokines that ultimately kill DA neurons in the substantia nigra in Parkinson disease (PD). Accordingly, recent data indicate that TLR4 is up-regulated by 1-methyl-4-phenyl-1,2,3,6- tetrahydropyridine (MPTP) treatment in a mouse model of PD. Here, we wished to evaluate the role of TLR4 in the acute mouse MPTP model of PD: TLR4-deficient mice and wild-type littermates control mice were used for the acute administration way of MPTP or a corresponding volume of saline. We demonstrate that TLR4-deficient mice are less vulnerable to MPTP intoxication than wild-type mice and display a decreased number of Iba1+ and MHC II+ activated microglial cells after MPTP application, suggesting that the TLR4 pathway is involved in experimental PD.
| Original language | English |
|---|---|
| Article number | 1393 |
| Journal | Scientific Reports |
| Volume | 3 |
| ISSN | 2045-2322 |
| DOIs | |
| Publication status | Published - 25.03.2013 |
Funding
C.N. was supported by a postdoctoral grant from the Deutsche Forschungsgemeinschaft, (DFG), Germany. D.A.F. was supported by a postdoctoral grant from the Michael J. Fox Foundation (MJFF) and a research grant of the University Medical Center Giessen and Marburg (UKGM). A.O. was supported by the Mildred-Scheel-Stiftung. T.L. was supported by a Master grant from the Fondation pour la Recherche Médicale (FRM). C.H. was supported by an M.D. thesis grant by the Boehringer Ingelheim Fond (BIF). E.C.H. and S.H. are investigators at the Centre National pour la Recherche Scientifique (CNRS). A.H. was supported by a ‘‘Poste Vert’’ (Accueil de Chercheurs Etrangers) from the Institut National de la Santé et de la Recherche Médicale (INSERM).
