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3-Acetylpyridine neurotoxicity in mice
L Wecker1, B Marrero-Rosado1, M E Engberg1
1Department of Psychiatry and Behavioral Neurosciences, University of South Florida Morsani College of Medicine, Tampa, FL, United States.
Neurotoxicology
|December 18, 2016
Summary
3-acetylpyridine (3-AP) causes neurotoxicity in mice, affecting balance and gait. Higher doses in mice, compared to rats, are needed to induce comparable motor deficits and neuronal loss in the inferior olive.
Area of Science:
- Neuroscience
- Animal Models
- Motor Control
Background:
- 3-acetylpyridine (3-AP) is a nicotinamide antagonist used to induce neurotoxicity.
- 3-AP causes cerebellar ataxia in rats by damaging the inferior olive neurons.
- Limited data exists on 3-AP's effects on mouse balance, gait, and its relationship to neuronal integrity.
Purpose of the Study:
- To characterize the effects of 3-AP on balance and gait in mice.
- To assess the impact of 3-AP on neuronal integrity in brain regions controlling motor coordination.
- To elucidate the relationship between 3-AP-induced inferior olive lesions and behavioral deficits.
Main Methods:
- Administration of 3-acetylpyridine to C57BL/6 mice.
- Quantification of balance and gait alterations.
- Assessment of neuronal loss (NeuN+ cells) in specific inferior olive subregions.
- Correlation analysis between neuronal counts and rotorod performance.
Main Results:
- C57BL/6 mice are less sensitive to 3-AP neurotoxicity than rats.
- A dose 6.5 times higher than used in rats produced comparable balance and gait deficits.
- Significant loss of NeuN+ neurons observed in multiple inferior olive subregions.
- Neuronal counts in most studied subregions correlated significantly with rotorod performance.
Conclusions:
- A specific high-dose regimen of 3-AP can effectively model ataxia in mice.
- 3-AP-induced neuronal loss in the inferior olive is linked to motor behavior deficits.
- This study provides a foundation for using 3-AP in mouse models of cerebellar dysfunction.
