Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease

• Published in: Scientific reports 2013-03, Vol.3 (1), p.1393, Article 1393
• Main Authors: Noelker, Carmen, Morel, Lydie, Lescot, Thomas, Osterloh, Anke, Alvarez-Fischer, Daniel, Breloer, Minka, Henze, Carmen, Depboylu, Candan, Skrzydelski, Delphine, Michel, Patrick P., Dodel, Richard C., Lu, Lixia, Hirsch, Etienne C., Hunot, Stéphane, Hartmann, Andreas
• Format: Article
• Language: English
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - adverse effects; 631/378/1689/1718; 631/378/1934; 631/378/2596/1953; 631/378/87; Animals; Cell death; Cell Death - genetics; Corpus Striatum - metabolism; Cytokines; Data processing; Dopamine - metabolism; Glial cells; Homovanillic Acid - metabolism; Humanities and Social Sciences; Inflammation; Intoxication; Life Sciences; Major histocompatibility complex; Mice; Mice, Knockout; Microglia; Microglia - metabolism; Movement disorders; MPTP; multidisciplinary; Neurodegenerative diseases; Neurons and Cognition; Parkinson's disease; Parkinsonian Disorders - genetics; Parkinsonian Disorders - metabolism; Rodents; Science; Signal transduction; Substantia nigra; TLR4 protein; Toll-Like Receptor 4 - genetics; Toll-Like Receptor 4 - metabolism; Toll-like receptors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep01393

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.