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Assessment of Sensorimotor Function in Mouse Models of Parkinson's Disease
Published on: June 17, 2013
Whether the Subacute MPTP-Treated Mouse is as Suitable as a Classic Model of Parkinsonism
Yue Qi1, Ziwei Zhang2, Yanning Li3
1Department of Human Anatomy, School of Basic Medical Sciences, Gannan Medical University, Harmonious Avenue, Zhang Gong District, Ganzhou, 341000, China.
Abstract:
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mice model is one of the most common animal models for Parkinson's disease (PD). It is classified into three types: acute, subacute, and chronic intoxication models. The subacute model has attracted much attention for its short period and similarity to PD. However, whether subacute MPTP intoxication in mouse mimics the movement and cognitive disorders of PD still remains highly controversial. Therefore, the present study reassessed the behavioral performances of subacute MPTP intoxication in mice using open field, rotarod, Y maze, and gait analysis at different time points (1, 7, 14, and 21 days) after modeling. Results of the current study showed that although MPTP-treated mice using subacute regimen showed severe dopaminergic neuronal loss and evident astrogliosis, they failed to display significant motor and cognitive deficits. Besides, expression of mixed lineage kinase domain-like (MLKL), a marker of necroptosis, was also significantly increased in the ventral midbrain and striatum of MPTP-intoxicated mice. This evidently implies that necroptosis may play an important role in MPTP-induced neurodegeneration. In conclusion, the findings of the present study suggest that subacute MPTP-intoxicated mice may not be a suitable model for studying parkinsonism. However, it can help in revealing the early pathophysiology of PD and studying the compensatory mechanisms which occur in early PD that prevent the emergence of behavioral deficits.
Insights
The subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model shows neurodegeneration but not motor or cognitive deficits typical of Parkinson's disease (PD). This model may reveal early PD pathophysiology rather than parkinsonism itself.
Area of Science:
- Neuroscience
- Pharmacology
- Pathology
Background:
- The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is widely used for Parkinson's disease (PD) research.
- Subacute MPTP intoxication models are favored for their brevity and resemblance to PD, but their efficacy in mimicking PD-related behavioral deficits is debated.
Purpose of the Study:
- To reassess the validity of the subacute MPTP mouse model in replicating motor and cognitive impairments characteristic of Parkinson's disease.
- To investigate the role of necroptosis in MPTP-induced neurodegeneration.
Main Methods:
- Mice were subjected to subacute MPTP intoxication.
- Behavioral assessments including open field, rotarod, Y-maze, and gait analysis were performed at multiple time points (1, 7, 14, 21 days).
- Neurodegeneration markers (dopaminergic neuronal loss, astrogliosis) and necroptosis marker (MLKL) expression were analyzed.
Main Results:
- MPTP-treated mice exhibited significant dopaminergic neuronal loss and astrogliosis.
- Despite neurodegeneration, no significant motor or cognitive deficits were observed in the subacute MPTP model.
- Increased expression of mixed lineage kinase domain-like (MLKL), a marker of necroptosis, was noted in key brain regions.
Conclusions:
- The subacute MPTP mouse model, while inducing neurodegeneration, may not accurately represent the motor and cognitive symptoms of clinical parkinsonism.
- This model could be valuable for studying the early neurodegenerative processes and compensatory mechanisms in Parkinson's disease.
- Necroptosis appears to be involved in MPTP-induced neurodegeneration, offering a potential target for therapeutic interventions.
