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.

journal_name

J Neurochem

authors

Alvarez-Fischer D,Guerreiro S,Hunot S,Saurini F,Marien M,Sokoloff P,Hirsch EC,Hartmann A,Michel PP

doi

10.1111/j.1471-4159.2008.05651.x

subject

Has Abstract

pub_date

2008-11-01 00:00:00

pages

701-11

issue

3

eissn

0022-3042

issn

1471-4159

pii

JNC5651

journal_volume

107

pub_type

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