Developmental Dieldrin Exposure Alters DNA Methylation at Genes Related to Dopaminergic Neuron Development and Parkinson’s Disease in Mouse Midbrain
| Autor: | Joseph Kochmanski, Alison I. Bernstein, Sarah E. VanOeveren, Joseph R. Patterson |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
Male
0301 basic medicine medicine.medical_specialty GRB10 Adaptor Protein Substantia nigra Biology Toxicology 03 medical and health sciences chemistry.chemical_compound Dieldrin Fetus 0302 clinical medicine Mesencephalon Dopamine Internal medicine medicine Animals Epigenetics Sex Characteristics Dieldrin Exposure and Dopamine Gene DNA Methylation Dopaminergic Neurons MPTP Parkinson Disease Methylation Epigenome DNA Methylation Mice Inbred C57BL 030104 developmental biology Endocrinology chemistry DNA methylation Female 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Toxicol Sci |
| ISSN: | 1096-0929 1096-6080 |
| DOI: | 10.1093/toxsci/kfz069 |
| Popis: | Human and animal studies have shown that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson’s disease (PD). Despite previous work showing a link between developmental dieldrin exposure and increased neuronal susceptibility to MPTP toxicity in male C57BL/6 mice, the mechanism mediating this effect has not been identified. Here, we tested the hypothesis that developmental exposure to dieldrin increases neuronal susceptibility via genome-wide changes in DNA methylation. Starting at 8 weeks of age and prior to mating, female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin by feeding (every 3 days) throughout breeding, gestation, and lactation. At 12 weeks of age, pups were sacrificed and ventral mesencephalon, containing primarily substantia nigra, was microdissected. DNA was isolated and dieldrin-related changes in DNA methylation were assessed via reduced representation bisulfite sequencing. We identified significant, sex-specific differentially methylated CpGs (DMCs) and regions (DMRs) by developmental dieldrin exposure (false discovery rate |
| Databáze: | OpenAIRE |
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