Disruption of dopamine transport by DDT and its metabolites

Abstract

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.

Persistent organochlorine pesticides in serum and risk of Parkinson disease

“…DDT and DDE can have dopaminergic effects in vitro, but they seem to be less toxic-at least in mice-to the dopaminergic system than dieldrin, and exposure in mice does not seem to produce nigrostriatal damage or behavioral abnormalities. 23 There is no data linking the fungicide HCB to PD.…”

In vitrodopaminergic neurotoxicity of pesticides: a link with neurodegeneration?

“…In other words, a herbicide targeting a plant-specific process that is absent in animals is perceived more safe than an insecticide targeting the nervous system of insects. From many insecticides it is known that they are indeed also neurotoxic in mammals, for example, organochlorine insecticides (Raymond-Delpech et al 2005;Hatcher et al 2008).…”

Parkinson's disease and pesticides: a toxicological perspective

“…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.…”