Parkinson’s disease (PD) is the fastest-growing neurological diseases worldwide, with increases outpacing aging and most rapid in recently industrialized areas, suggesting the role of environmental factors. Together, epidemiological studies, post-mortem analysis and mechanistic studies suggest that exposure to persistent organic pollutants, including the organochlorine pesticide dieldrin, increases PD risk. In mouse models, developmental dieldrin exposure causes male-specific exacerbation of neuronal susceptibility to MPTP and synucleinopathy. Specifically, developmental dieldrin exposure induces male-specific exacerbation of toxicity in the α-synuclein (α-syn) pre-formed fibril (PFF) model with increased deficits in striatal dopamine (DA) turnover and motor deficits on the challenging beam. Here, we hypothesized that alterations in DA handling contribute to the observed changes and assessed vesicular monoamine transporter 2 (VMAT2) function and DA release in this dieldrin/PFF two-hit model. Female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin or vehicle every 3 days by feeding, starting at 8 weeks of age by ingestion and continuing throughout breeding, gestation, and lactation. Male offspring from independent litters underwent unilateral, intrastriatal injections of α-syn PFFs at 12 weeks of age and vesicular ³H-DA uptake assays and fast-scan cyclic voltammetry (FSCV) were performed at 4 months post-PFF injection. We observed a dieldrin-induced increase in DA release in striatal slices in PFF-injected animals, but no change in VMAT2 activity. These results suggest that developmental dieldrin exposure increases a compensatory response to synucleinopathy-triggered striatal DA loss and supports our hypothesis that alterations in DA handling may underly the observed exacerbation of PFF-induced deficits in motor behavior and DA turnover.

GraphPad Prism files (pzfx) can be opened in GraphPad Prism or 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. 

AxioScan czi files can be opened in Zeiss Zen software (proprietary) or ImageJ (open source)

Raw data from FSCV experiments (tdms and txt files) requires Python (open source) and Demon Voltammetry and Analysis Software (free license from Wake Forest Innovations).

csv files can be opened in a spreadsheet software or text editor