Nest building performance following MPTP toxicity in mice
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Thomas Nikolaj Sager1, Jeppe Kirchhoff, Arne Mørk
1H Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. TSA@lundbeck.com
Abstract:
Systemic injection of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) in mice is one of the primary models used to evaluate neuroprotective and symptomatic treatment strategies for Parkinson's disease. Many behavioral methods for evaluation of MPTP toxicity have been described, but they often involve challenging scenarios that require handling and transfer of animals to novel environments and in some cases prior animal training. These factors can profoundly influence animal behavior and potentially influence experimental outcome. Presented here is a new nest building scoring paradigm based on the animals' normal home cage behavior that is a simple, non-invasive, and reproducible measure for estimating neurological dysfunction in MPTP intoxicated mice. Nest building behavior requires orofacial and forelimb movement and has been shown to be dopamine-dependent making it a possible method for assessing parkinsonian-like symptoms. Significant deficits in nest building scores after 2x20 and 2x25 mg/kg MPTP coincided with a 90% reduction in striatal dopamine. Nest building deficits could be detected for more than a week after intoxication. However, after 28 days the change in behavior was no longer detected, which may reflect the plasticity of the tyrosine hydroxylase positive neurons in the dorsolateral part of striatum.
Insights
A novel nest building test in mice offers a simple, non-invasive method to assess Parkinson's disease (PD) models. This approach effectively measures neurological deficits caused by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) exposure.
Area of Science:
- Neuroscience
- Pharmacology
- Animal Models
Background:
- 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model is crucial for Parkinson's disease (PD) research.
- Existing behavioral assessments for MPTP toxicity can be invasive, require animal training, and introduce confounding variables.
- A need exists for simpler, non-invasive methods to evaluate PD-like symptoms in MPTP-treated mice within their home environment.
Purpose of the Study:
- To introduce and validate a novel nest building scoring paradigm as a non-invasive measure of neurological dysfunction in MPTP-intoxicated mice.
- To assess the correlation between nest building deficits and dopamine levels in the striatum.
- To determine the duration of detectable nest building deficits post-MPTP intoxication.
Main Methods:
- MPTP was administered systemically to mice at doses of 2x20 mg/kg and 2x25 mg/kg.
- Nest building behavior was scored within the animals' home cages.
- Striatal dopamine levels were measured.
- Nest building performance was assessed at various time points post-MPTP administration.
Main Results:
- Significant deficits in nest building scores were observed following MPTP intoxication.
- These behavioral deficits correlated with a substantial (90%) reduction in striatal dopamine.
- Nest building impairments were detectable for over a week, but normalized by 28 days post-intoxication.
Conclusions:
- Nest building is a sensitive, non-invasive behavioral indicator of parkinsonian-like symptoms in MPTP-treated mice.
- This paradigm offers a reproducible and home-cage-based method for evaluating neuroprotective and symptomatic treatments for Parkinson's disease.
- The observed recovery may reflect neural plasticity in dopaminergic pathways, suggesting potential for endogenous repair mechanisms.
