Murine Motor and Behavior Functional Evaluations for Acute 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Intoxication
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Acute intoxication with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induces nigrostriatal neurodegeneration that reflects Parkinson’s disease (PD) pathobiology. The model is commonly used for rodent studies of PD pathogenesis and diagnostics and for developmental therapeutics. However, tests of motor function in MPTP-intoxicated mice have yielded mixed results. This unmet need reflects, in part, lesion severity, animal variability, and the overall test sensitivity and specificity. In attempts to standardize rodent motor function and behavioral tests, mice were trained on the rotarod or habituated in an open field test chamber, and baseline performance measurements were collected prior to MPTP intoxication. One week following MPTP intoxication, motor function and behavior were assessed and baseline measurements applied to post-MPTP measurements with normalization to PBS controls. Rotarod and open field tests assessed in this manner demonstrated significant differences between MPTP- and saline-treated mice, while tests of neuromuscular strength and endurance did not. We conclude that the rotarod and open field tests provide reliable measures of motor function for MPTP-intoxicated mice.
KeywordsParkinson’s disease MPTP Behavior Mice Rotarod Open field Grooming
We would like to thank Megan Willer and Alex Braun for help with data collection; Rebecca Banerjee, Adelina Holguin, and Kalipada Pahan for advice on experimental methods and design; and Stephen Bonasera for discussions that enhanced the depth of this work. This work is supported by NIH grants 2R01 NS034239, P20 RR15635, P30 AI42845, P01 DA028555, P20 RR15635, and 5R01 NS36126, 1R01 NS070190, 1 P01 NS043985-01, P01 MH64570, 1R01 MH083516, P20 DA026146, and PO1 NS31492.
The authors have no financial conflict of interest.
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