Organochlorine compounds in human brain

Corrigan, F.M.; French, M. C.; Murray, Lauren K

doi:10.1177/096032719601500314

Cited by 41 publications

(28 citation statements)

References 10 publications

(5 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Research over the last several decades has provided a wealth of support for exposure to environmental chemicals, including organochlorine insecticides as a risk factor for PD (Hatcher et al , 2008). Indeed, levels of organochlorine compounds, such as dieldrin and β-HCH have been found to be elevated in the brain tissue and serum, respectively, of PD patients and have been shown in laboratory studies to damage the nigtrostriatal dopamine system (Corrigan et al , 1996; Corrigan et al , 2000; Kitazawa et al , 2001; Kitazawa et al , 2004; Hatcher et al , 2007; Richardson et al , 2009; Richardson et al , 2011). In addition to these compounds, a recent epidemiological study also identified exposure to the organochlorine insecticide, endosulfan, as a risk factor for PD (Rhodes et al , 2013).…”

Section: Introductionmentioning

confidence: 99%

Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring

et al. 2014

View full text Add to dashboard Cite

The contribution of environmental toxicants to the etiology and risk of Parkinson’s disease (PD) has been clearly established, with organochlorine insecticides routinely shown to damage the nigrostriatal dopamine pathway. Although PD is generally considered an adult onset disease, it has been postulated that exposure to environmental contaminants or other factors early in life during critical periods of neurodevelopment could alter the dopaminergic circuit and predispose individuals to developing PD. Recent epidemiological evidence has found exposure to the organochlorine insecticide endosulfan to be a risk factor for PD. However, the specific dopaminergic targets or vulnerable developmental time points related to endosulfan exposure have not been investigated. Thus, we sought to investigate dopaminergic neurotoxicity following developmental exposure to endosulfan as well as following an additional challenge with MPTP. Our in vitro findings demonstrate a reduction in SK-N-SH cells and ventral mesencephalic primary cultures after endosulfan treatment. Using an in vivo developmental model, exposure to endosulfan during gestation and lactation caused a reduction in DAT and TH in the striatum of male offspring. These alterations were exacerbated following subsequent treatment with MPTP. In contrast, exposure of adult mice to endosulfan did not elicit dopaminergic damage and did not appear to increase the vulnerability of the dopamine neurons to MPTP. These findings suggest that development during gestation and lactation represents a critical window of susceptibility to endosulfan exposure and development of the nigrostriatal dopamine system. Furthermore, these exposures appear to sensitize the dopamine neurons to additional insults that may occur later in life.

show abstract

Section: Introductionmentioning

confidence: 99%

Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring

et al. 2014

View full text Add to dashboard Cite

show abstract

“…Available epidemiological studies point towards an increased risk associated with insecticides (in particular organochlorine insecticides; Elbaz et al 2009;Freire & Koifman 2012) and herbicides (Pezzoli & Cereda 2013). Interestingly, the epidemiological evidence for the involvement of organochlorine insecticides is underlined by biomarkers of exposure in serum (Weisskopf et al 2010) and post mortem detection of elevated levels of particular organochlorine insecticides in brains of PD patients (Corrigan et al 1996;Corrigan et al 2000).…”

Section: The Role Of Pesticides In Pdmentioning

confidence: 99%

In vitrodopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Heusinkveld

Berg

Westerink

2014

Veterinary Quarterly

View full text Add to dashboard Cite

“…Thus, human exposure to dieldrin continues via contaminated food (Corrigan et al, 1996). Studies indicate that exposure to dieldrin is closely associated with Parkinson's disease (Fleming et al, 1994;Corrigan et al, 2000).…”

mentioning

confidence: 99%

Environmental Neurotoxic Pesticide Increases Histone Acetylation to Promote Apoptosis in Dopaminergic Neuronal Cells: Relevance to Epigenetic Mechanisms of Neurodegeneration

Song¹,

Anantharam²,

Sun³

et al. 2010

Mol Pharmacol

189

126

View full text Add to dashboard Cite

Pesticide exposure has been implicated in the etiopathogenesis of Parkinson's disease (PD); in particular, the organochlorine insecticide dieldrin is believed to be associated with PD. Emerging evidence indicates that histone modifications play a critical role in cell death. In this study, we examined the effects of dieldrin treatment on histone acetylation and its role in dieldrin-induced apoptotic cell death in dopaminergic neuronal cells. In mesencephalic dopaminergic neuronal cells, dieldrin induced a time-dependent increase in the acetylation of core histones H3 and H4. Histone acetylation occurred within 10 min of dieldrin exposure indicating that acetylation is an early event in dieldrin neurotoxicity. The hyperacetylation was attributed to dieldrin-induced proteasomal dysfunction, resulting in accumulation of a key histone acetyltransferase (HAT), cAMP response element-binding protein. The novel HAT inhibitor anacardic acid significantly attenuated dieldrin-induced histone acetylation, Protein kinase C ␦ proteolytic activation and DNA fragmentation in dopaminergic cells protected against dopaminergic neuronal degeneration in primary mesencephalic neuronal cultures. Furthermore, 30-day exposure of dieldrin in mouse models induced histone hyperacetylation in the striatum and substantia nigra. For the first time, our results collectively demonstrate that exposure to the neurotoxic pesticide dieldrin induces acetylation of core histones because of proteasomal dysfunction and that hyperacetylation plays a key role in dopaminergic neuronal degeneration after exposure of dieldrin.

show abstract

Organochlorine compounds in human brain

Cited by 41 publications

References 10 publications

Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring

Developmental exposure to the organochlorine insecticide endosulfan damages the nigrostriatal dopamine system in male offspring

In vitrodopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

Environmental Neurotoxic Pesticide Increases Histone Acetylation to Promote Apoptosis in Dopaminergic Neuronal Cells: Relevance to Epigenetic Mechanisms of Neurodegeneration

Contact Info

Product

Resources

About