title: Modelling Parkinson-like neurodegeneration via osmotic minipump delivery of MPTP and probenecid.
abstract: Mouse models of MPTP intoxication have been used extensively to explore the molecular mechanisms of Parkinson's disease. However, these models present some limitations since; (i) Dopaminergic (DA) cell death occurs rapidly in contrast to the presumably slow evolution of the disease process. (ii) Some of the key histological features of the disease such as Lewy body like inclusions and long-term inflammatory changes are lacking. Fornai et al. [Proc. Natl Acad. Sci. USA 102 (2005), 3413] suggested that continuous delivery of MPTP with Alzet osmotic minipumps may possibly circumvent these problems. Our results show, however, that MPTP infusion via Alzet osmotic minipumps (40 mg/kg/day) produces only a transient depletion in striatal dopamine (DA) without causing dopaminergic cell loss in the substantia nigra. Neuronal cell loss occurred, however, if MPTP was infused concomitantly with probenecid, an uricosuric agent which potentiates the effects of the toxin injected via the i.p. route. Even under these conditions, dopaminergic cell loss was moderate (-25%) and other neurodegenerative changes characteristic of Parkinson's disease remained undetectable.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, Unité Mixte de Recherche S679, Paris, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Alvarez-Fischer
authors.forename: Serge
authors.initials: S
authors.lastname: Guerreiro
authors.forename: Stéphane
authors.initials: S
authors.lastname: Hunot
authors.forename: Françoise
authors.initials: F
authors.lastname: Saurini
authors.forename: Marc
authors.initials: M
authors.lastname: Marien
authors.forename: Pierre
authors.initials: P
authors.lastname: Sokoloff
authors.forename: Etienne C
authors.initials: EC
authors.lastname: Hirsch
authors.forename: Andreas
authors.initials: A
authors.lastname: Hartmann
authors.forename: Patrick P
authors.initials: PP
authors.lastname: Michel