title: Toll like receptor 4 mediates cell death in a mouse MPTP model of Parkinson disease.
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.
authors: INSERM UMR_S975, Université Pierre et Marie Curie Paris 06 UMR_S975, CNRS UMR 7225, CR-ICM, Groupe Hospitalier Pitié-Salpêtrière, 75013 Paris, France.
authors: Carmen
authors: C
authors: Noelker
authors: Lydie
authors: L
authors: Morel
authors: Thomas
authors: T
authors: Lescot
authors: Anke
authors: A
authors: Osterloh
authors: Daniel
authors: D
authors: Alvarez-Fischer
authors: Minka
authors: M
authors: Breloer
authors: Carmen
authors: C
authors: Henze
authors: Candan
authors: C
authors: Depboylu
authors: Delphine
authors: D
authors: Skrzydelski
authors: Patrick P
authors: PP
authors: Michel
authors: Richard C
authors: RC
authors: Dodel
authors: Lixia
authors: L
authors: Lu
authors: Etienne C
authors: EC
authors: Hirsch
authors: Stéphane
authors: S
authors: Hunot
authors: Andreas
authors: A
authors: Hartmann
mesh_terms: D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine / Q000009:adverse effects; D000818:Animals; D016923:Cell Death / Q000235:genetics; D003342:Corpus Striatum / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D006719:Homovanillic Acid / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D017628:Microglia / Q000378:metabolism; D020734:Parkinsonian Disorders / Q000235:genetics / Q000378:metabolism*; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism*
chemical_list: D051197:Toll-Like Receptor 4; D015632:1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine; D004298:Dopamine; D006719:Homovanillic Acid