Mouse model of Parkinsonism: a comparison between subacute MPTP and chronic MPTP/probenecid treatment
Section snippets
Animals
Eight- to 10-week-old, male, C57BL/6 mice (Charles River Laboratories, Wilmington, MA, USA), weighing 22–25 g at the beginning of the study, were housed two to five animals per cage with food pellets and water available ad libitum. The room was maintained at constant temperature and humidity on a 12-h light–dark cycle. A minimum number of mice required to produce reliable scientific data was used in this study. All animal treatments including anesthesia were carried out strictly according to
Striatal dopamine levels
The striatal DA contents among respective control groups in subacute and chronic studies did not differ significantly and thus, data arising from animals in those groups were pooled. As shown in Fig. 1A, 3 days after the subacute MPTP treatment, the loss of striatal DA was highly significant (76% loss). Thirty days after the treatment, the loss of striatal DA remained significant but to a lesser extent (53% loss) when compared to controls, suggesting that a partial recovery had occurred.
Discussion
In order to identify the pathophysiological mechanisms of PD and to develop new strategies for neuroprotection, it is imperative to establish a long-term animal model that closely resembles human Parkinsonism. This report presents a close correlation between neurochemical, morphological and behavioral manifestations validating a new model of MPTP Parkinsonism in a single study. We provide evidence that, for 6 months after chronic MPTP/probenecid treatment, C57BL mice exhibit a marked depletion
Conclusion
We have shown that the chronic treatment of mice with MPTP/probenecid is accompanied by sustained nigrostriatal degeneration and motor decline resembling human PD. Based on the comparisons made in this study, this chronic model is an improvement over the conventional acute and subacute models. The chronic MPTP/probenecid model has a potential for explorations of disease progression, mechanisms of neurodegeneration, and neuroprotection.
Acknowledgements
The authors thank Dr. P.L. Gabbott for providing the StereoInvestigator apparatus and Charlie Callison, Katy Schafbuch and Shari Buzolich for their technical contributions to the work. This research was supported in part by grants from the University of Missouri Research Board, the Health Future Foundation, Inc., the National Parkinson Foundation, Inc. (to Y.-S.L.), and the National Institute of Neurological Disorders and Stroke (R01 NS41799 to G.E.M., Y.-S.L. and S.T.).
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