Data for: Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of α-synuclein-preformed fibril-induced toxicity and motor deficits

This dataset contains all data for published figures and supplementary figures in the manuscript "Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of α-synuclein-preformed fibril-induced toxicity and motor deficits".
GraphPad Prism files can be viewed in the free Viewer mode or data can be extracted by viewing files in a text editor. R and RStudio are freely available for running Rmd files. file_list.txt includes a list of all files included in this dataset

Abstract: Human and animal studies have shown that exposure to the organochlorine pesticide dieldrin is
associated with increased risk of Parkinson’s disease (PD). Previous work showed that
developmental dieldrin exposure increased neuronal susceptibility to MPTP toxicity in male
C57BL/6 mice, possibly via changes in dopamine (DA) packaging and turnover. However, the
relevance of the MPTP model to PD pathophysiology has been questioned. We therefore
studied dieldrin-induced neurotoxicity in the α-synuclein (α-syn)-preformed fibril (PFF) model,
which better reflects the α-syn pathology and toxicity observed in PD pathogenesis. Specifically,
we used a “two-hit” model to determine whether developmental dieldrin exposure increases
susceptibility to α-syn PFF-induced synucleinopathy. Dams were fed either dieldrin (0.3 mg/kg,
every 3-4 days) or vehicle corn oil starting 1 month prior to breeding and continuing through
weaning of pups at postnatal day 22. At 12 weeks of age, male and female offspring received
intrastriatal PFF or control saline injections. Consistent with the male-specific increased
susceptibility to MPTP, our results demonstrate that developmental dieldrin exposure
exacerbates PFF-induced toxicity in male mice only. Specifically, in male offspring, dieldrin
exacerbated PFF-induced motor deficits on the challenging beam and increased DA turnover in
the striatum 6 months after PFF injection. However, male offspring showed neither
exacerbation of phosphorylated α-syn (pSyn) aggregation in the substantia nigra (SN) at 1 or 2
months post-PFF injection, nor exacerbation of PFF-induced TH and NeuN loss in the SN 6
months post-PFF injection. Collectively, these data indicate that developmental dieldrin
exposure produces a male-specific increase in neuronal vulnerability to synucleinopathy. This
sex-specific result is consistent with both previous work in the MPTP model, our previously
reported sex-specific effects of this exposure paradigm on the male and female epigenome, and
the higher prevalence and more severe course of PD in males. The novel two-hit environmental
toxicant/PFF exposure paradigm established in this project can be used to explore the
mechanisms by which other PD-related exposures alter neuronal vulnerability to
synucleinopathy in sporadic PD.