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Protocol for the MPTP mouse model of Parkinson's disease

Abstract

This protocol describes our method of producing a reliable mouse model of Parkinson's disease (PD) using the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We discuss the particulars of the model, provide key references and outline what investigators need to know to develop the MPTP mouse model of PD safely and successfully. Completion of this protocol depends on the regimen of MPTP used and on the actual planned studies, which often range from 7 to 30 d. This protocol calls for implementation of safety measures and for the acquisition of several pieces of equipment, which are a one-time investment worth making if one elects to use this model on a regular basis.

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Figure 1: Mouse brain levels of dopamine (DA) and its main metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC) and homovanillic acid (HVA).
Figure 2: Immunostaining of tyrosine hydroxylase (TH)–positive neurons in the substantia nigra pars compacta (SNpc) and terminals in the striatum.
Figure 3: MPTP and MPP+ quantification in blood and brain tissues.

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Acknowledgements

The authors wish to thank Drs. Cristina Malagelada Grau, Delphine Prou, Du-Chu Wu, Diane Re and Chun Zhou for their insightful comments on this manuscript. The authors wish to acknowledge the support of the National Institutes of Health (NIH)/National Institute of Neurological Disorders and Stroke Grants R01 NS42269, P50 NS38370 and P01 NS11766; NIH/National Institute of Aging Grant AG R01 21617; National Institute of Environmental Health Sciences Grant ES013177; US Department of Defense Grant DAMD 17-03-1; the Parkinson's Disease Foundation Grant CU51523606, and the Muscular Dystrophy Association/Wings-over-Wall Street.

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Correspondence to Serge Przedborski.

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Supplementary information

Supplementary Data

MPTP Core Experiment Log (PDF 15 kb)

Supplementary Information

MPTP Core Experiment Log (PDF 19 kb)

Supplementary Video

Mouse brain dissection tutorial (MOV 61856 kb)

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Jackson-Lewis, V., Przedborski, S. Protocol for the MPTP mouse model of Parkinson's disease. Nat Protoc 2, 141–151 (2007). https://doi.org/10.1038/nprot.2006.342

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