Data from: Developmental exposure to the Parkinson’s disease-associated organochlorine pesticide dieldrin alters dopamine neurotransmission in α-synuclein pre-formed fibril (PFF)-injected mice

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.