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Neurochemical findings in the MPTP model of Parkinson's disease
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Neurochemical findings in the MPTP model of Parkinson's disease
N. Schmidt1 and B. Ferger1
| (1) |
Institute of Pharmacology and Toxicology, Faculty of Pharmacy, University of Marburg, Federal Republic of Germany, DE |
| (2) |
Behavioural Neurobiology Laboratory, Swiss Federal Institute of Technology Zürich, Schwerzenbach, Switzerland, CH |
Summary. Animal models are a very important approach to study the pathogenesis and therapeutic intervention strategies of human diseases.
Since many human disorders do not arise spontaneously in animals, characteristic functional changes have to be mimicked by
neurotoxic agents. For instance, the application of the dopaminergic neurotoxin MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine)
is able to produce striking similarities to Parkinson's disease (PD) diagnosed in humans. MPTP is thought to selectively damage
dopaminergic neurons predominantly those originating in the substantia nigra pars compacta (SNc) which leads to impaired dopaminergic
neurotransmission accompanied by a loss of dopaminergic nerve terminals in the striatum. MPTP-induced neurochemical, behavioral,
and histopathological alterations replicate very closely the clinical symptoms of PD patients, which will be discussed in
this paper and render the MPTP model currently the most favored PD model to study therapeutic intervention strategies in an
easy and reliable way in preclinical studies.
We and many other research groups propose that the knowledge about the neurotoxic mechanisms of MPTP such as mitochondrial
dysfunction with breakdown of energy metabolism and free radical production will help us to understand the underlying mechanisms
of PD, which are not fully understood yet. In particular, the novel aspects of inflammatory processes and the involvement
of reactive nitrogen species in addition to reactive oxygen species seem to be important milestones for a better understanding
of the neurodegenerative effects of MPTP.
In this review we focus on the MPTP mouse model which is easy practicable and widely used in neuroscience research and draw
comparisons to the human pathology in PD.
Keywords: Animal models - MPTP - neurodegeneration - neurotoxicity - Parkinson's disease.
Received March 1, 2001; accepted July 11, 2001
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