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Text
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<a href="http://doi.org/10.1016/j.nbd.2020.104947" target="_blank" rel="noreferrer noopener">http://doi.org/10.1016/j.nbd.2020.104947</a>
Pages
104947
Volume
141
ISSN
1095-953X 0969-9961
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Update Year & Number
June 2020 Update II
NEOMED College
NEOMED College of Pharmacy
NEOMED Department
Department of Pharmaceutical Sciences
NEOMED Student Publications
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Title
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Developmental exposure to the organochlorine pesticide dieldrin causes male-specific exacerbation of alpha-synuclein-preformed fibril-induced toxicity and motor deficits.
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Neurobiology of disease
Date
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2020
2020-05-15
Subject
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Neuroinflammation; Neurotoxicity; Parkinson's; Pesticide; Sex differences; Synuclein
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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
Description
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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
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<a href="http://doi.org/10.1016/j.nbd.2020.104947" target="_blank" rel="noreferrer noopener">10.1016/j.nbd.2020.104947</a>
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journalArticle
2020
Bernstein Alison I
Cole-Strauss Allyson
Department of Pharmaceutical Sciences
Fleming Sheila M
Gezer Aysegul O
Herman Danielle E
journalArticle
June 2020 Update II
Kemp Christopher J
Kochmanski Joseph
Kuhn Nathan C
Lipton Jack W
Luk Kelvin C
McIntire Alyssa
Miller Kathryn M
NEOMED College of Pharmacy
NEOMED College of Pharmacy Student
NEOMED Student Publications
Neurobiology of disease
Neuroinflammation
Neurotoxicity
Parkinson's
Patterson Joseph R
Pesticide
Sex differences
Sortwell Caryl E
Synuclein
VanOeveren Sarah E