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The overall rod performance test in the MPTP-treated-mouse model of Parkinsonism
G Rozas1, E López-Martín, M J Guerra
1Department of Morphological Sciences, Faculty of Medicine, University of Santiago de Compostela, Spain.
Abstract:
We investigated the usefulness of the Overall Rotarod Performance (ORP) test for evaluating overall locomotory ability in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-injected-mouse model of Parkinson's disease (PD). For this procedure, the mice are pretrained on the rotarod and then tested at a series of increasing speeds, recording the time that the animal remains on the rod at each speed; the overall rod performance (ORP) of each animal is then calculated as the area under the curve in a plot of time-on-the-rod against rotation speed. At 15-day intervals, C57BL/6 mice were injected (or sham-injected) with MPTP, with ORP testing 7-10 days after each injection. After the fourth injection (day 45), mice in the treated group showed clearly lower ORP than mice in the control group (70-90% reduction in ORP), and were thus considered effectively lesioned. Subsequently, we investigated the short-term effects of apomorphine and L-DOPA on ORP in MPTP-treated mice. Apomorphine (at 0.5 or 2.5 mg/kg) had no significant effect, while L-DOPA (at 80 but not at 40 mg/kg) caused almost complete short-term recovery of pretreatment ORP. By about 100 days after the last MPTP injection, MPTP-treated mice showed partial long-term recovery of ORP; at this stage the mice were killed for tyrosine hydroxylase (TH) immunohistochemistry studies. TH immunoreactivity in the striatum showed a strong positive correlation with ORP as tested on day 100. We conclude that the ORP test is useful for evaluating motor deficit in MPTP-treated mice, and the effects of subsequent treatments.
Insights
The Overall Rotarod Performance (ORP) test effectively measures motor deficits in the MPTP-mouse model of Parkinson's disease (PD). L-DOPA treatment showed significant short-term recovery of motor function in these mice.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Models
Background:
- Parkinson's disease (PD) is a neurodegenerative disorder characterized by motor deficits.
- The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is widely used to study PD.
- Evaluating motor function in preclinical models is crucial for assessing therapeutic interventions.
Purpose of the Study:
- To assess the utility of the Overall Rotarod Performance (ORP) test for quantifying motor impairment in the MPTP-induced PD mouse model.
- To investigate the short-term and long-term effects of pharmacological treatments on motor function in MPTP-treated mice.
- To correlate rotarod performance with striatal tyrosine hydroxylase (TH) immunoreactivity.
Main Methods:
- C57BL/6 mice were repeatedly injected with MPTP to induce Parkinsonian symptoms.
- Overall Rotarod Performance (ORP) was measured by calculating the area under the curve of time-on-rod versus rotation speed.
- MPTP-treated mice received apomorphine or L-DOPA to evaluate drug effects on ORP, followed by TH immunohistochemistry.
Main Results:
- MPTP injection led to a significant reduction (70-90%) in ORP, indicating substantial motor deficits.
- L-DOPA (80 mg/kg) significantly improved ORP in the short term, while apomorphine had no significant effect.
- MPTP-treated mice exhibited partial long-term recovery of ORP, which positively correlated with striatal TH levels.
Conclusions:
- The ORP test is a valuable tool for assessing motor deficits and treatment efficacy in the MPTP-mouse model of PD.
- L-DOPA demonstrates potential for short-term motor function recovery in this PD model.
- ORP serves as a reliable indicator of dopaminergic neurodegeneration, as evidenced by its correlation with TH immunoreactivity.