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Murine Motor and Behavior Functional Evaluations for Acute 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Intoxication

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Abstract

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.

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Acknowledgments

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.

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The authors have no financial conflict of interest.

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Authors and Affiliations

  1. Department of Pharmacology and Experimental Neuroscience, University of Nebraska Medical Center, Omaha, NE, 68198, USA

    Jessica A. L. Hutter-Saunders, Howard E. Gendelman & R. Lee Mosley

  2. University of Nebraska Medical Center, 985930 Nebraska Medical Center, Omaha, NE, 68198-5930, USA

    Howard E. Gendelman

Authors
  1. Jessica A. L. Hutter-Saunders
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  2. Howard E. Gendelman
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  3. R. Lee Mosley
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Corresponding author

Correspondence to Howard E. Gendelman.

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Supplemental Fig. 1

MPTP-induced affect on stride length. Mice were treated with PBS or four injections of MPTP at 18, 20, 22, and 24 mg/kg/injection. One week after treatment, the stride lengths of mice were measured using the ink paw print test on a white papered gangway leading into the home cage. Mean stride lengths were determined for four to six mice/group and significant differences among means were determined by one-way ANOVA and pair-wise comparisons determined by Tukey’s HSD post hoc analysis where a p ≤ 0.05 compared to PBS. No significant differences in stride length were detected. (GIF 27 kb)

High resolution image (TIFF 1623 kb)

Supplemental Fig. 2

MPTP-induced affect on syntactic grooming. One week after PBS or MPTP treatment (four injections of 18 mg/kg/injection of MPTP), each mouse was videotaped for 10 min and later scored by an observer, blinded to treatment. Significant difference between means was determined by Student’s t test where a p ≤ 0.05. The number of completed syntactic grooming chains in MPTP-intoxicated mice trended below those observed in PBS-injected controls (p = 0.15). (GIF 8 kb)

High resolution image (TIFF 1999 kb)

Examples of syntactic grooming in PBS-treated and MPTP-intoxicated mice, 7 days post-treatment. (MP4 3727 kb)

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Hutter-Saunders, J.A.L., Gendelman, H.E. & Mosley, R.L. Murine Motor and Behavior Functional Evaluations for Acute 1-Methyl-4-Phenyl-1,2,3,6-Tetrahydropyridine (MPTP) Intoxication. J Neuroimmune Pharmacol 7, 279–288 (2012). https://doi.org/10.1007/s11481-011-9269-4

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