Neuroscience, 2001-01, Vol.106 (3), p.589-601
2001
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- Autor(en) / Beteiligte
- Titel
- Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment
- Ist Teil von
- Neuroscience, 2001-01, Vol.106 (3), p.589-601
- Ort / Verlag
- Oxford: Elsevier Ltd
- Erscheinungsjahr
- 2001
- Quelle
- Access via ScienceDirect (Elsevier)
- Beschreibungen/Notizen
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is widely used to induce an animal model of Parkinsonism. The conventional mouse model, which usually involves acute or subacute injections of MPTP, results in a significant but reversible loss of dopaminergic functions. We have developed an alternative mouse model, in which co-administration of MPTP with probenecid results in the chronic loss of striatal dopamine for at least 6 months after cessation of treatment. In the present study, we compare the neurochemical, morphological and behavioral changes that occur in this alternative, chronic model with those in the conventional, subacute model. In the chronic model, we demonstrate an almost 80% loss of striatal dopamine and dopamine uptake 6 months after withdrawal from treatment. The neurochemical signs match unbiased stereological measures that demonstrate gradual loss of substantia nigra neurons. Rotarod performance further substantiates these findings by showing a progressive decline in motor performance. Based on the comparisons made in this study in mice, the chronic MPTP/probenecid model shows considerable improvements over the conventional, subacute MPTP model. The sustained alterations in the nigrostriatal pathway resemble the cardinal signs of human Parkinson’s disease and suggest that this chronic mouse model is potentially useful to study the pathophysiology and mechanisms of Parkinsonism. It should also prove useful for the development of neuroprotection strategies.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0306-4522eISSN: 1873-7544DOI: 10.1016/S0306-4522(01)00295-0Titel-ID: cdi_proquest_miscellaneous_18368638
- Format
- –
- Schlagworte
- 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine - pharmacology, Acute Disease, Animals, Axons - drug effects, Axons - metabolism, Axons - pathology, Biological and medical sciences, Brain - drug effects, Brain - pathology, Brain - physiopathology, Cell Death - drug effects, Cell Death - physiology, Chronic Disease, Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases, Disease Models, Animal, dopamine, Dopamine - metabolism, Dopamine - physiology, Dopamine Agents - pharmacology, Drug Administration Schedule, Immunohistochemistry, Male, Medical sciences, Mice, Mice, Inbred C57BL - metabolism, Motor Activity - drug effects, Motor Activity - physiology, Neostriatum - drug effects, Neostriatum - metabolism, Neostriatum - pathology, Neurology, Neurotoxins - pharmacology, Nucleus Accumbens - drug effects, Nucleus Accumbens - metabolism, Nucleus Accumbens - pathology, Parkinsonian Disorders - metabolism, Parkinsonian Disorders - pathology, Parkinsonian Disorders - physiopathology, Probenecid - pharmacology, rotarod, stereology, striatum, substantia nigra, Substantia Nigra - drug effects, Substantia Nigra - metabolism, Substantia Nigra - pathology, Tyrosine 3-Monooxygenase - metabolism, tyrosine hydroxylase, Uricosuric Agents - pharmacology