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| Status |
Public on May 31, 2024 |
| Title |
Developmental origins of Parkinson’s disease risk: developmental exposure to the organochlorine pesticide dieldrin leads to sex-specific DNA modifications in critical neurodevelopmental pathways in the mouse midbrain |
| Organism |
Mus musculus |
| Experiment type |
Methylation profiling by high throughput sequencing
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| Summary |
Epidemiological studies show that exposure to the organochlorine pesticide dieldrin is associated with increased risk of Parkinson’s disease (PD). Animal studies support a link between developmental dieldrin exposure and increased neuronal susceptibility in the α-synuclein preformed fibril (α-syn PFF) and MPTP models in adult male C57BL/6 mice. In a previous study, we showed that developmental dieldrin exposure was associated with sex-specific changes in DNA modifications within genes related to dopaminergic neuron development and maintenance at 12 weeks of age. Here, we used capture hybridization-sequencing with custom baits to interrogate DNA modifications across the entire genetic loci of the previously identified genes at multiple time points – birth, 6 weeks, 12 weeks, and 36 weeks old. We identified largely sex-specific dieldrin-induced changes in DNA modifications at each time point that annotated to pathways important for neurodevelopment, potentially related to critical steps in early neurodevelopment, dopaminergic neuron differentiation, synaptogenesis, synaptic plasticity, and glial-neuron interactions. Despite large numbers of age-specific DNA modifications, longitudinal analysis identified a small number of DMCs with dieldrin-induced deflection of epigenetic aging. The sex-specificity of these results adds to evidence that sex-specific responses to PD-related exposures may underly sex-specific differences in disease. Overall, these data support the idea that developmental dieldrin exposure leads to changes in epigenetic patterns that persist after the exposure period has ended and disrupt critical neurodevelopmental pathways and that developmental exposures can impact risk of late life diseases, including PD.
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| Overall design |
Capture hybridization data for developmental dieldrin exposure study with 4 follow-up timepoints in exposed offspring: birth, 6 weeks old, 12 weeks old, and 36 weeks old. At each timepoint (and across the later 3 timepoints), we compared control (n=8-10 per sex) vs. dieldrin treatment (0.3 mg/kg) (n=8-10 per sex) using the DSS R package.
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| Contributor(s) |
Kochmanski J, Virani M, Kuhn NC, Boyd SL, Adams M, Becker K, Bernstein AI |
| Citation(s) |
38746441 |
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| Submission date |
Apr 16, 2024 |
| Last update date |
Jun 01, 2024 |
| Contact name |
Alison I Bernstein |
| Organization name |
Rutgers University
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| Department |
Pharmacology and Toxicology
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| Street address |
170 Freylinghuysen Rd
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| City |
Piscataway |
| State/province |
NJ |
| ZIP/Postal code |
08854 |
| Country |
USA |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (150)
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| Relations |
| BioProject |
PRJNA1101082 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE264165_RAW.tar |
354.0 Mb |
(http)(custom) |
TAR (of COV) |
SRA Run Selector |
| Raw data are available in SRA |
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