Diorthosubstituted Polychlorinated Biphenyls in Caudate Nucleus in Parkinson's Disease

Corrigan, F.M.; Murray, Lauren K; Wyatt, C.L.; Shore, Richard F.

doi:10.1006/exnr.1998.6776

Cited by 170 publications

(114 citation statements)

References 12 publications

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“…Although there are some reports of higher levels of DDT or its main metabolite DDE in the postmortem brain tissue of PD patients [52,53], there has been no experimental evidence to support the role of DDT or DDE in PD pathogenesis [54], suggesting that these compounds might be markers of exposure to other, more toxic compounds. Although concerns over hexachlorocyclohexanes (HCHs) have arisen, including several groups lobbying to have lindane added to the list of 12 persistent organic pollutants banned by the Stockholm Convention and reporting higher levels of lindane in the postmortem PD brain tissue [55], there is little experimental evidence to support a role in PD.…”

Section: Organochlorinesmentioning

confidence: 99%

“…Also, many of these in vitro studies used concentrations much higher than one would expect to observe in human tissue. Finally, several studies have reported increased levels of dieldrin in the postmortem brain tissue of PD patients versus age-matched controls [53,55]. Heptachlor, which contaminated the milk supply in Oahu, Hawaii in the 1980s, also exhibits some neurotoxic effects on the dopamine system [66][67][68][69], but it has not been associated with PD in any human studies.…”

Section: Organochlorinesmentioning

confidence: 99%

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Parkinson's disease and pesticides: a toxicological perspective

Hatcher

Pennell

Miller

2008

Trends in Pharmacological Sciences

295

176

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Environmental factors have been shown to contribute to the incidence of Parkinson's disease (PD). Pesticides, which represent one of the primary classes of environmental agents associated with PD, share the common feature of being intentionally released into the environment to control or eliminate pests. Pesticides consist of multiple classes and subclasses of insecticides, herbicides, rodenticides, fungicides, fumigants and others and exhibit a vast array of chemically diverse structures. In this review we examine the evidence regarding the ability of each of the major pesticide subclasses to increase the incidence of PD. We propose that, from a toxicological perspective, it would be beneficial to identify specific subclasses, common structural features and the propensity for widespread human exposure when considering the potential role in PD, rather than using the overly broad term of 'pesticides' to describe this diverse group of chemicals. Furthermore, these chemicals and their environmentally relevant combinations should be evaluated for their ability to promote or accelerate PD and not merely for being singular causative agents.

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Section: Organochlorinesmentioning

confidence: 99%

Section: Organochlorinesmentioning

confidence: 99%

Parkinson's disease and pesticides: a toxicological perspective

Hatcher

Pennell

Miller

2008

Trends in Pharmacological Sciences

295

176

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“…Specifically for Parkinson's disease, risk factors include rural living, well-water consumption, pesticide exposure, and exposure to solvents (85,86). PCBs are elevated in brains of Parkinson's disease patients (87), as are dieldrin (88) and lindane (89). Exposure to paraquat has been reported to cause a 3.6-fold increase in the risk of developing Parkinson's disease (90).…”

Section: Neurodegenerative Diseasesmentioning

confidence: 99%

Understanding the human health effects of chemical mixtures.

Carpenter

Arcaro

Spink

2002

Environ Health Perspect

329

198

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Most research on the effects of chemicals on biologic systems is conducted on one chemical at a time. However, in the real world people are exposed to mixtures, not single chemicals. Although various substances may have totally independent actions, in many cases two substances may act at the same site in ways that can be either additive or nonadditive. Many even more complex interactions may occur if two chemicals act at different but related targets. In the extreme case there may be synergistic effects, in which case the effects of two substances together are greater than the sum of either effect alone. In reality, most persons are exposed to many chemicals, not just one or two, and therefore the effects of a chemical mixture are extremely complex and may differ for each mixture depending on the chemical composition. This complexity is a major reason why mixtures have not been well studied. In this review we attempt to illustrate some of the principles and approaches that can be used to study effects of mixtures. By the nature of the state of the science, this discussion is more a presentation of what we do not know than of what we do know about mixtures. We approach the study of mixtures at three levels, using specific examples. First, we discuss several human diseases in relation to a variety of environmental agents believed to influence the development and progression of the disease. We present results of selected cellular and animal studies in which simple mixtures have been investigated. Finally, we discuss some of the effects of mixtures at a molecular level.

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“…These findings are supported by numerous animal studies that have identified potential mechanistic links between pesticides and PD pathogenesis (Betarbet et al, 2000;Bloomquist et al, 2002;Caudle et al, 2005;Hatcher et al, 2007;Kitazawa et al, 2001Kitazawa et al, , 2003McCormack et al, 2005;Miller et al, 1999;Purkerson-Parker et al, 2001;Richardson et al, 2006;Thiruchelvam et al, 2003). Additionally, higher levels of pesticides have been identified in post-mortem PD brains versus age-matched controls (Corrigan et al, 1998(Corrigan et al, , 2000Fleming et al, 1994;Pennell et al, 2006).…”

Section: Introductionmentioning

confidence: 80%

“…We selected a range of concentrations that were relevant to, or slightly higher than, the levels to which humans may have been exposed (Chu et al, 2003;Corrigan et al, 1998Corrigan et al, , 2000Fleming et al, 1994). This same approach, utilized in our dieldrin exposure studies, resulted in several pathological changes that were comparable to those seen in PD (Hatcher et al, 2007).…”

Section: Discussionmentioning

confidence: 99%

Disruption of dopamine transport by DDT and its metabolites

et al. 2008

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Epidemiological studies suggest a link between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Although studies have been unable to clearly identify specific pesticides that contribute to PD, a few human studies have reported higher levels of the organochlorine pesticides dieldrin and DDE (a metabolite of DDT) in post-mortem PD brains. Previously, we found that exposure of mice to dieldrin caused perturbations in the nigrostriatal dopamine system consistent with those seen in PD. Given the concern over the environmental persistence and reintroduction of DDT for the control of malaria-carrying mosquitoes and other pests, we sought to determine whether DDT and its two major metabolites, DDD and DDE, could damage the dopamine system. In vitro analyses in mouse synaptosomes and vesicles demonstrated that DDT and its metabolites inhibit the plasma membrane dopamine transporter (DAT) and the vesicular monoamine transporter (VMAT2). However, exposure of mice to either DDT or DDE failed to show evidence of nigrostriatal damage or behavioral abnormalities in any of the measures examined. Thus, we report that in vitro effects of DDT and its metabolites on components of the dopamine system do not translate into neurotoxicological outcomes in orally exposed mice and DDT appears to have less dopamine toxicity when compared to dieldrin. These data suggest elevated DDE levels in PD patients may represent a measure of general pesticide exposure and that other pesticides may be responsible for the association between pesticide exposure and PD.

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Diorthosubstituted Polychlorinated Biphenyls in Caudate Nucleus in Parkinson's Disease

Cited by 170 publications

References 12 publications

Parkinson's disease and pesticides: a toxicological perspective

Parkinson's disease and pesticides: a toxicological perspective

Understanding the human health effects of chemical mixtures.

Disruption of dopamine transport by DDT and its metabolites

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