Aldrin and Dieldrin: A Review of Research on Their Production, Environmental Deposition and Fate, Bioaccumulation, Toxicology, and Epidemiology in the United States

Jorgenson, J. Lisa

doi:10.2307/3434852

Cited by 37 publications

(30 citation statements)

References 48 publications

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“…However, the health effects of past exposures will continue for decades as the population currently diagnosed with PD and those who will develop PD in the next 20-30 years were likely exposed to dieldrin prior to its phase out. 21,[26][27][28] Furthermore, well-established experimental models of dieldrin exposure have demonstrated that dieldrin induces oxidative stress, is selectively toxic to dopaminergic cells, disrupts striatal dopamine (DA) activity, and may promote α-syn aggregation. 20,21,[29][30][31][32][33][34] Because of the established association of dieldrin with PD risk and well-characterized animal exposure dosing paradigms, our lab utilizes the developmental dieldrin exposure as a representative model of increased PD susceptibility.…”

Section: Introductionmentioning

confidence: 99%

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

Gezer

Kochmanski

VanOeveren

et al. 2020

Preprint

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Highlights• Developmental dieldrin exposure increases α-syn-PFF-induced motor deficits • Developmental dieldrin exposure increases PFF-induced deficits in DA handling • Developmental dieldrin exposure does not affect PFF-induced loss of nigral neurons • This is a novel paradigm modeling how environmental factors increase risk of PD • Female mice show PFF-induced pathology, but no PFF-induced motor deficits. AbstractHuman 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. KeywordsParkinson's, pesticide, synuclein, neurotoxicity, neuroinflammation, sex differences resistant. Over time, the α-syn aggregates progressively compact and eventually lead to neuronal degeneration. 38,39,45,46 Thus, the intrastriatal injection of α-syn PFFs can be used to model pathological synucleinopathy and nigrostriatal toxicity in mice. Here...

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Section: Introductionmentioning

confidence: 99%

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

Gezer

Kochmanski

VanOeveren

et al. 2020

Preprint

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“…Dieldrin is a highly toxic organochlorine pesticide that was phased out of commercial use in the 1970s, but has persisted in the environment due to its high stability and lipophilicity (CDC, 2016). Given these properties, dieldrin accumulates in lipid-rich tissues like the brain, and has been classified as a persistent organic pollutant (Corrigan et al, 2000;Jorgenson, 2001;Kanthasamy et al, 2005). Previous epidemiology studies have shown a positive association between dieldrin exposure and PD risk (Kanthasamy et al, 2005;Moretto and Colosio, 2011), and mechanistic animal research has shown that adult and developmental dieldrin exposures are associated with oxidative stress, disrupted expression of PD-related proteins, and increased susceptibility of dopaminergic neurons to toxicants that target the dopaminergic system (Richardson et al, 2006;Hatcher et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Developmental Dieldrin Exposure Alters DNA Methylation at Genes Related to Dopaminergic Neuron Development and Parkinson’s Disease in Mouse Midbrain

Kochmanski

VanOeveren

Bernstein

2018

Preprint

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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). Despite previous work showing a link between developmental dieldrin exposure and increased neuronal susceptibility to MPTP toxicity in male C57BL/6 mice, the mechanism mediating this effect has not been identified. Here, we tested the hypothesis that developmental exposure to dieldrin increases neuronal susceptibility via genome-wide changes in DNA methylation. Starting at 8 weeks of age and prior to mating, female C57BL/6 mice were exposed to 0.3 mg/kg dieldrin by feeding (every 3 days) throughout breeding, gestation, and lactation. At 12 weeks of age, pups were sacrificed and midbrains were dissected. DNA was isolated and dieldrin-related changes in DNA methylation were assessed via reduced representation bisulfite sequencing (RRBS). We identified significant, sex-specific differentially methylated CpGs (DMCs) and regions (DMRs) by developmental dieldrin exposure (FDR<0.05), including DMCs at the Nr4a2 and Lmx1b genes, which are involved in dopaminergic neuron development and maintenance. Developmental dieldrin exposure had distinct effects on the male and female epigenome. Furthermore, a separate set of changes in DNA methylation was identified after adult exposure to dieldrin, suggesting that adult and developmental dieldrin toxicity may not act through a shared epigenetic mechanism. Together, our data suggest that developmental dieldrin exposure establishes sex-specific poised epigenetic states early in life. These poised epigenomes may mediate sensitivity to additional environmental stimuli and contribute to the development of late-life neurodegenerative disease, including PD.

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“…The OCP dieldrin (1,2,3,4,10,10-hexachloro-6,7-epoxy-1,4,4a,5,6,7,8,8a-octahydro-1,4,5,8-dimethanonaphthalene) remains persistent in sediment in agricultural regions where it was previously used despite being banned over 30 years ago in North America. Jorgenson (2001) reported that dieldrin, and the related pesticide aldrin, were ranked second behind DDT in agricultural use in the United States in the 1960s and dieldrin was used on approximately 90 crop species that included corn, hay, rye, and oat. Many OCPs are transported into aquatic ecosystems via runoff from these agricultural sites, and in some cases, dieldrin continues to be detected in close proximity to these sites at levels high enough to pose a risk to aquatic organisms.…”

Section: Introductionmentioning

confidence: 99%

Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

et al. 2010

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Exposure to dieldrin induces neurotoxic effects in the vertebrate CNS and disrupts reproductive processes in teleost fish. Reproductive impairment observed in fish by dieldrin is likely the result of multiple effects along the hypothalamic-pituitary-gonadal axis but the molecular signaling cascades are not well characterized. To better elucidate the mode of action of dieldrin in the hypothalamus, this study measured neurotransmitter levels and examined the transcriptomic response in female largemouth bass (LMB) to an acute treatment of dieldrin. Male and female LMB were injected with either vehicle or 10 mg dieldrin/kg and sacrificed after seven days. There were no significant changes in dopamine or DOPAC concentrations in the neuroendocrine brain of males and females after treatment but GABA levels in females were moderately increased 20–30% in the hypothalamus and cerebellum. In the female hypothalamus, there were 227 transcripts (p<0.001) identified as being differentially regulated by dieldrin. Functional enrichment analysis revealed transcription, DNA repair, ubiquitin-proteasome pathway, and cell communication, as biological processes over-represented in the microarray analysis. Pathway analysis identified DNA damage, inflammation, regeneration, and Alzheimer’s disease as major cell processes and diseases affected by dieldrin. Using multiple bioinformatics approaches, this study demonstrates that the teleostean hypothalamus is a target for dieldrin-induced neurotoxicity and provides mechanistic evidence that dieldrin activates similar cell pathways and biological processes that are also associated with the etiology of human neurological disorders.

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Aldrin and Dieldrin: A Review of Research on Their Production, Environmental Deposition and Fate, Bioaccumulation, Toxicology, and Epidemiology in the United States

Cited by 37 publications

References 48 publications

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

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

Developmental Dieldrin Exposure Alters DNA Methylation at Genes Related to Dopaminergic Neuron Development and Parkinson’s Disease in Mouse Midbrain

Effects of acute dieldrin exposure on neurotransmitters and global gene transcription in largemouth bass (Micropterus salmoides) hypothalamus

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