Pesticides and Parkinson's disease

Couteur, David G. Le; McLean, Allan J.; Taylor, Matthew C.; Woodham, Benjamin L.; Board, Philip G.

doi:10.1016/s0753-3322(99)80077-8

Cited by 190 publications

(101 citation statements)

References 92 publications

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“…Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing PD Le Couteur et al, 1999;Priyadarshi et al, 2000;Semchuk et al, 1991Semchuk et al, ,1992. In addition, a correlation between the presence of the organochlorine insecticide, dieldrin, in the brain and diagnosis of PD has been reported (Fleming et al, 1994).…”

Section: Nih Public Accessmentioning

confidence: 99%

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Hatcher

Richardson

Guillot

et al. 2007

Experimental Neurology

129

101

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Numerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing Parkinson's disease (PD). Here, we provide evidence that the insecticide dieldrin causes specific oxidative damage in the nigrostriatal dopamine (DA) system. We report that exposure of mice to low levels of dieldrin for 30 days resulted in alterations in dopamine-handling as evidenced by a decrease in dopamine metabolites, DOPAC (31.7% decrease) and HVA (29.2% decrease) and significantly increased cysteinyl-catechol levels in the striatum. Furthermore, dieldrin resulted in a 53% decrease in total glutathione, an increase in the redox potential of glutathione, and a 90% increase in protein carbonyls. α-Synuclein protein expression was also significantly increased in the striatum (25% increase). Finally, dieldrin caused a significant decrease in striatal expression of the dopamine transporter as measured by 3 H-WIN 35,428 binding and 3 H-dopamine uptake. These alterations occurred in the absence of dopamine neuron loss in the substantia nigra pars compacta. These effects represent the ability of low doses of dieldrin to increase the vulnerability of nigrostriatal dopamine neurons by inducing oxidative stress and suggest that pesticide exposure may act as a promoter of PD. *Corresponding Author: Gary W. Miller, Ph.D., Emory University -Center for Neurodegenerative Disease, Whitehead Biomedical Research Building 505K, 615 Michael Street Atlanta, GA 30322, Phone: 404.712.8582, Fax: 404.727.3728, Email: gary.miller@emory.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Parkinson's disease (PD) is a chronic, progressive neurological disorder clinically characterized by resting tremor, bradykinesia, postural instability and rigidity (Marsden, 1984). Pathologically, PD presents as dopaminergic neuronal loss in the substantia nigra pars compacta (SNc), striatal depletion of the neurotransmitter dopamine (DA), the loss of neurochemical markers, such as the dopamine transporter (DAT), and the presence of Lewy bodies containing α-synuclein (Spillantini et al., 1997). Because only 5-10% of PD cases are thought to be primarily genetic in origin, investigation of the role of environmental factors in the pathogenesis of the disease is warranted (Dauer & Przedborski, 2003). NIH Public AccessNumerous epidemiological studies have shown an association between pesticide exposure and an increased risk of developing PD Le Couteur et al., 1999;Priyadarshi et al., 2000;Semchuk et al., 1991Semchuk et al., ,1992. In addition, a correlation between the presence of th...

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Section: Nih Public Accessmentioning

confidence: 99%

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Hatcher

Richardson

Guillot

et al. 2007

Experimental Neurology

129

101

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“…There is significant epidemiological evidence supporting an association between pesticide exposure and an increased risk of PD (Ascherio et al, 2006;Kanthasamy et al, 2005;Le Couteur et al, 1999;Priyadarshi et al, 2000;Semchuk et al, 1991Semchuk et al, , 1992. However, the specific compounds that contribute to this risk have yet to be identified.…”

Section: Discussionmentioning

confidence: 99%

“…Epidemiological studies suggest a link between pesticide exposure and an increased risk of developing Parkinson's disease (PD; Ascherio et al, 2006;Frigerio et al, 2006;Gorell et al, 1998;Le Couteur et al, 1999;Priyadarshi et al, 2001Priyadarshi et al, , 2000Semchuk et al, 1991Semchuk et al, , 1992. 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).…”

Section: Introductionmentioning

confidence: 97%

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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“…The abusive and indiscriminate use of chemical insecticides is responsible for environmental and ecological damage to natural enemies and the death of millions of birds and fishes along with the insect-pests (18,29). In addition, there is strong epidemiological (17,27) and experimental (1,42) evidence linking the occurrence of cancer, Parkinson's disease and others neurological disorders to pesticide exposure. Thus, it is important at this juncture to identify and characterize novel compounds with insecticidal activity.…”

Section: Introductionmentioning

confidence: 99%

Heterologous expression of an insecticidal gene from the armed spider (Phoneutria nigriventer)

Figueiredo¹,

Kalapothakis²,

Gomez³

et al. 2008

J. Venom. Anim. Toxins incl. Trop. Dis

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Insect-pests are global problems that cause severe damage to crop plants, and their control is commonly based on chemical insecticides. However, negative effects of pesticides on the environment and human health emphasize the necessity to develop alternative methods for insect-pest control. In the present study, a gene coding for the insecticidal peptide TX4(6-1) of the Brazilian armed spider (Phoneutria nigriventer) was cloned in fusion with maltose binding protein (MBP) and expressed in Escherichia coli. The affinity purified protein MBP-GlyTX4 was cleaved with the Xa factor and used for a bioassay against Spodoptera frugiperda and rabbit immunization. Five micrograms GlyTX4 protein injected into the hemocoel of larvae and abdominal cavity of adults produced trembling and uncoordinated movements immediately after injection and all adult insects died after 12h. After two days, larvae became paralyzed and the epidermal color changed to dark brown. Furthermore, the development stage was prolonged for two weeks. Alternatively, slices of maize leaves were imbibed with 15 micrograms of the recombinant protein cleaved with the Xa factor and used as diet for larvae. In this experiment, all larvae died in about 30 minutes. Polyclonal antibodies anti-MBP-GlyTX4 were effective for recognizing MBP and GlyTX4 in whole cell extract from E. coli expressing the recombinant protein.

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Pesticides and Parkinson's disease

Cited by 190 publications

References 92 publications

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Dieldrin exposure induces oxidative damage in the mouse nigrostriatal dopamine system

Disruption of dopamine transport by DDT and its metabolites

Heterologous expression of an insecticidal gene from the armed spider (Phoneutria nigriventer)

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