Geography, Drinking Water Chemistry, Pesticides and Herbicides and the Etiology of Parkinson's Disease

Rajput, Ali H.; Uitti, Ryan J.; Stern, Walter G.; Laverty, W. H.; O’Donnell, Kate; O’Donnell, Denise; Yuen, WH; Dua, Anish

doi:10.1017/s0317167100037823

Cited by 134 publications

(79 citation statements)

References 18 publications

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“…PQ is one of the possible herbicides that are involved in PD, since a strong correlation has been found between the incidence of the disease and the amount of PQ used (Lanska, 1997;Liou et al, 1997;Rajput et al, 1987;Ritz and Yu, 2000).…”

Section: Discussionmentioning

confidence: 99%

“…Paraquat (1,1'-dimethyl-4,4'-bipyridinium, PQ), is widely used as a non-selective herbicide, and bears structural similarity to 1-methyl-4-phenyl pyridinium (MPP + ). This herbicide adversely impacts on dopamine systems, and a strong geographical overlapping has been found between the incidence of PD and the amount of PQ used (Lanska, 1997;Liou et al, 1997;Rajput et al, 1987;Ritz and Yu, 2000). PQ induces dopaminergic neuronal damage in experimental animals (Corasaniti et al, 1992;Corasaniti et al, 1998).…”

Section: Introductionmentioning

confidence: 99%

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Paraquat leads to dopaminergic neural vulnerability in organotypic midbrain culture

Shimizu

Matsubara

Ohtaki

et al. 2003

Neuroscience Research

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Paraquat (PQ) is a herbicide to possibly induce Parkinson's disease (PD), since a strong correlation has been found between the incidence of the disease and the amount of paraquat used. In this study, we examined PQ toxicity in rat organotypic midbrain slice cultures.PQ dose dependently reduced the number of dopaminergic neurons in cultured slices.Since this damage was prevented by GBR-12909, the dopamine transporter could be an initial step of the PQ induced dopaminergic neurotoxicity. The sequential treatments with lower PQ and MPP + doses, where each dose alone was not lethal, markedly killed dopamine neurons, suggesting that the exposure of a lower dose of PQ could lead to the vulnerability of dopaminergic neurons. This cell death was prevented by the inhibitors of NMDA, nitric oxide synthase (NOS), cycloheximide and caspase cascade. Neurons expressing NOS were identified inside and around the regions where dopamine neurons were packed. The cell death induced by the sequential treatments with PQ and MPP + was also rescued by Ldeprenyl and dopamine D2/3 agonists. These results strongly support that the constant exposure to low levels of PQ would lead to the vulnerability of dopaminergic neurons in the nigrostriatal system by the excitotoxic pathway, and might potentiate neurodegeneration caused by the exposure of other substances and aging.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Paraquat leads to dopaminergic neural vulnerability in organotypic midbrain culture

Shimizu

Matsubara

Ohtaki

et al. 2003

Neuroscience Research

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“…Parkinson's disease (PD), a profound movement disorder resulting from nigrostriatal dopaminergic (DA) system degeneration, has been linked to living in a rural environment, farming, drinking well water, and occupational exposure to agricultural chemicals, suggesting an environmental exposure basis for the disease (Rajput et al, 1987;Semchuk et al, 1992;Liou et al, 1997;Gorell et al, 1998;. Correspondingly, a recent comprehensive study of over 19,000 white male twins showed that genetic heritability is not the basis of sporadic PD with onset over age 50 .…”

Section: Abstract: Dopamine; Striatum; Nucleus Accumbens; Substantiamentioning

confidence: 99%

The Nigrostriatal Dopaminergic System as a Preferential Target of Repeated Exposures to Combined Paraquat and Maneb: Implications for Parkinson's Disease

et al. 2000

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Experimental evidence supporting 1,1Ј-dimethyl-4,4Ј-bipyridinium [paraquat (PQ)] as a risk factor for Parkinson's disease (PD) is equivocal. Other agricultural chemicals, including dithiocarbamate fungicides such as manganese ethylenebisdithiocarbamate [maneb (MB)], are widely used in the same geographical regions as paraquat and also impact dopamine systems, suggesting that mixtures may be more relevant etiological models. This study therefore proposed that combined PQ and MB exposures would produce greater effects on dopamine (DA) systems than would either compound administered alone. Male C57BL/6 mice were treated twice a week for 6 weeks with intraperitoneal saline, 10 mg/kg paraquat, 30 mg/kg maneb, or their combination (PQ ϩ MB). MB, but not PQ, reduced motor activity immediately after treatment, and this effect was potentiated by combined PQ ϩ MB treatment. As treatments progressed, only the combined PQ ϩ MB group evidenced a failure of motor activity levels to recover within 24 hr. Striatal DA and dihydroxyphenylacetic acid increased 1-3 d and decreased 7 d after injections. Only PQ ϩ MB reduced tyrosine hydroxylase (TH) and DA transporter immunoreactivity and did so in dorsal striatum but not nucleus accumbens. Correspondingly, striatal TH protein levels were decreased only by combined PQ ϩ MB 5 d after injection. Reactive gliosis occurred only in response to combined PQ ϩ MB in dorsal-medial but not ventral striatum. TH immunoreactivity and cell counts were reduced only by PQ ϩ MB and in the substantia nigra but not ventral tegmental area. These synergistic effects of combined PQ ϩ MB, preferentially expressed in the nigrostriatal DA system, suggest that such mixtures could play a role in the etiology of PD.

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“…Other studies have demonstrated that drinking well-water and living in a rural setting, both of which may increase exposure to agricultural pesticides, increase the risk of developing PD (Rajput et al, 1986;Barbeau et al, 1987;Rajput et al, 1987;Golbe et al, 1990;Semchuk et al, 1991). In addition, exposure to pesticides used in the home has been linked to PD (Stephenson, 2000).…”

mentioning

confidence: 99%

Pyrethroid pesticide-induced alterations in dopamine transporter function

Elwan

Richardson

Guillot

et al. 2006

Toxicology and Applied Pharmacology

103

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Parkinson's disease (PD) is a progressive neurodegenerative disease affecting the nigrostriatal dopaminergic pathway. Several epidemiological studies have demonstrated an association between pesticide exposure and the incidence of PD. Studies from our laboratory and others have demonstrated that certain pesticides increase levels of the dopamine transporter (DAT), an integral component of dopaminergic neurotransmission and a gateway for dopaminergic neurotoxins. Here, we report that repeated exposure (3 injections over 2 weeks) of mice to two commonly used pyrethroid pesticides, deltamethrin (3 mg/kg) and permethrin (0.8 mg/kg), increases DATmediated dopamine uptake by 31 and 28%, respectively. Using cells stably expressing DAT, we determined that exposure (10 min) to deltamethrin and permethrin (1 nM-100 μM) had no effect on DAT-mediated dopamine uptake. Extending exposures to both pesticides for 30 min (10 μM) or 24 h (1, 5, and 10 μM) resulted in significant decrease in dopamine uptake. This reduction was not the result of competitive inhibition, loss of DAT protein, or cytotoxicity. However, there was an increase in DNA fragmentation, an index of apoptosis, in cells exhibiting reduced uptake at 30 min and 24 h. These data suggest that up-regulation of DAT by in vivo pyrethroid exposure is an indirect effect and that longer-term exposure of cells results in apoptosis. Since DAT can greatly affect the vulnerability of dopamine neurons to neurotoxicants, up-regulation of DAT by deltamethrin and permethrin may increase the susceptibility of dopamine neurons to toxic insult, which may provide insight into the association between pesticide exposure and PD. KeywordsDeltamethrin; Permethrin; Pyrethroid; Dopamine transporter; Parkinson's disease Parkinson's disease (PD) is a disabling neurodegenerative disorder characterized by the loss of nigrostriatal dopamine neurons and the formation of intraneuronal inclusions termed Lewy bodies (Olanow and Tatton, 1999). Although the exact etiology of PD is unknown, both genetic and environmental factors are thought to contribute to the pathogenesis of PD. While there are rare instances of genetically-linked PD, data from a recent comprehensive

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Geography, Drinking Water Chemistry, Pesticides and Herbicides and the Etiology of Parkinson's Disease

Cited by 134 publications

References 18 publications

Paraquat leads to dopaminergic neural vulnerability in organotypic midbrain culture

Paraquat leads to dopaminergic neural vulnerability in organotypic midbrain culture

The Nigrostriatal Dopaminergic System as a Preferential Target of Repeated Exposures to Combined Paraquat and Maneb: Implications for Parkinson's Disease

Pyrethroid pesticide-induced alterations in dopamine transporter function

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