Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of alpha-synuclein-preformed fibril-induced toxicity and motor deficits.

Title

Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of alpha-synuclein-preformed fibril-induced toxicity and motor deficits.

Creator

Gezer Aysegul O; Kochmanski Joseph; VanOeveren Sarah E; Cole-Strauss Allyson; Kemp Christopher J; Patterson Joseph R; Miller Kathryn M; Kuhn Nathan C; Herman Danielle E; McIntire Alyssa; Lipton Jack W; Luk Kelvin C; Fleming Sheila M; Sortwell Caryl E; Bernstein Alison I

Publisher

Neurobiology of disease

Date

2020
2020-05-15

Description

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 alpha-synuclein (alpha-syn)-preformed fibril (PFF) model, which better reflects the alpha-syn pathology and toxicity observed in PD pathogenesis. Specifically, we used a "two-hit" model to determine whether developmental dieldrin exposure increases susceptibility to alpha-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 alpha-syn 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

Subject

Neuroinflammation; Neurotoxicity; Parkinson's; Pesticide; Sex differences; Synuclein

Rights

Article information provided for research and reference use only. All rights are retained by the journal listed under publisher and/or the creator(s).

Format

journalArticle

Search for Full-text

Users with a NEOMED Library login can search for full-text journal articles at the following url: https://libraryguides.neomed.edu/home

Pages

104947

Volume

141

ISSN

1095-953X 0969-9961

NEOMED College

NEOMED College of Pharmacy

NEOMED Department

Department of Pharmaceutical Sciences
NEOMED Student Publications

Update Year & Number

June 2020 Update II

Citation

Gezer Aysegul O; Kochmanski Joseph; VanOeveren Sarah E; Cole-Strauss Allyson; Kemp Christopher J; Patterson Joseph R; Miller Kathryn M; Kuhn Nathan C; Herman Danielle E; McIntire Alyssa; Lipton Jack W; Luk Kelvin C; Fleming Sheila M; Sortwell Caryl E; Bernstein Alison I, “Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of alpha-synuclein-preformed fibril-induced toxicity and motor deficits.,” NEOMED Bibliography Database, accessed September 25, 2021, https://neomed.omeka.net/items/show/11098.

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