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Paraoxonase 2 deficiency in mice alters motor behavior and causes region-specific transcript changes in the brain
- Source :
- Neurotoxicol Teratol
- Publication Year :
- 2021
- Publisher :
- Elsevier BV, 2021.
-
Abstract
- Paraoxonase 2 (PON2) is an intracellular antioxidant enzyme shown to play an important role in mitigating oxidative stress in the brain. Oxidative stress is a common mechanism of toxicity for neurotoxicants and is increasingly implicated in the etiology of multiple neurological diseases. While PON2 deficiency increases oxidative stress in the brain in-vitro, little is known about its effects on behavior in-vivo and what global transcript changes occur from PON2 deficiency. We sought to characterize the effects of PON2 deficiency on behavior in mice, with an emphasis on locomotion, and evaluate transcriptional changes with RNA-Seq. Behavioral endpoints included home-cage behavior (Noldus PhenoTyper), motor coordination (Rotarod) and various gait metrics (Noldus CatWalk). Home-cage behavior analysis showed PON2 deficient mice had increased activity at night compared to wildtype controls and spent more time in the center of the cage, displaying a possible anxiolytic phenotype. PON2 deficient mice had significantly shorter latency to fall when tested on the rotarod, suggesting impaired motor coordination. Minimal gait alterations were observed, with decreased girdle support posture noted as the only significant change in gait with PON2 deficiency. Beyond one home-cage metric, no significant sex-based behavioral differences were found in this study. Finally, A subset of samples were utilized for RNA-Seq analysis, looking at three discrete brain regions: cerebral cortex, striatum, and cerebellum. Highly regional- and sex-specific changes in RNA expression were found when comparing PON2 deficient and wildtype mice, suggesting PON2 may play distinct regional roles in the brain in a sex-specific manner. Taken together, these findings demonstrates that PON2 deficiency significantly alters the brain on both a biochemical and phenotypic level, with a specific impact on motor function. These data have implications for future gene-environment toxicological studies and warrants further investigation of the role of PON2 in the brain.
- Subjects :
- Male
medicine.medical_specialty
Cerebellum
medicine.drug_class
Striatum
Motor Activity
Biology
Toxicology
medicine.disease_cause
Anxiolytic
Article
Mice
Cellular and Molecular Neuroscience
Developmental Neuroscience
Internal medicine
medicine
Animals
Sex Characteristics
Behavior, Animal
Aryldialkylphosphatase
Brain
Phenotype
Corpus Striatum
Motor coordination
Oxidative Stress
medicine.anatomical_structure
Endocrinology
Cerebral cortex
Toxicity
Female
Oxidative stress
Subjects
Details
- ISSN :
- 08920362
- Volume :
- 87
- Database :
- OpenAIRE
- Journal :
- Neurotoxicology and Teratology
- Accession number :
- edsair.doi.dedup.....b1585e9c24fdf9ba64f3c72c3409dddb