Neurochemical findings in the MPTP model of Parkinson's disease

• Published in: Journal of Neural Transmission Vol. 108; no. 11; pp. 1263 - 1282
• Main Authors: SCHMIDT, N, FERGER, B
• Format: Journal Article
• Language: English
• Published: Wien Springer 01.01.2001; New York, NY
• Subjects: 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - administration & dosage; Animals; Behavior, Animal - drug effects; Biological and medical sciences; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Models, Animal; Dopamine Agents - toxicity; Humans; Medical sciences; Mice; MPTP Poisoning - metabolism; MPTP Poisoning - physiopathology; Neurology; Parkinson Disease - metabolism; Parkinson Disease - physiopathology; Parkinson Disease, Secondary - chemically induced; reactive nitrogen species; Toxin; Animal model; Nervous system diseases; Central nervous system disease; Neurotoxin; Parkinson disease; Degenerative disease; Review; Cerebral disorder; Extrapyramidal syndrome
• DOI: 10.1007/s007020100004
• ISSN: 0300-9564

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.