A Case-Control Study of Parkinson's Disease in Urban Population of Southern Israel

Herishanu, Y.; Medvedovski, Mordechai; Goldsmith, John R.; Kordysh, Ella

doi:10.1017/s0317167100052835

Cited by 56 publications

(50 citation statements)

References 19 publications

(20 reference statements)

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“…Results from a number of epidemiological and case-controlled studies appear to indicate a positive correlation between early exposure to pesticides and development of PD (Gorell et al, 1998;Ritz and Yu, 2000;Herishanu et al, 2001). Experimentally, several groups have reported recently that administration of pesticides and/or related agrochemicals results in the degeneration of the nigrostriatal dopaminergic pathway.…”

Section: Discussionmentioning

confidence: 99%

“…Among the various environmental factors suspected to play a role in the pathogenesis of PD, exposure to agrochemicals has been most intensely investigated (Gorell et al, 1998;Ritz and Yu, 2000;Herishanu et al, 2001;Priyadarshi et al, 2001). A number of groups have reported that administration of herbicides such as rotenone and paraquat induces parkinsonism in rodents (Betarbet et al, 2000;Thiruchelvam et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

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Synergistic Dopaminergic Neurotoxicity of the Pesticide Rotenone and Inflammogen Lipopolysaccharide: Relevance to the Etiology of Parkinson's Disease

et al. 2003

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Parkinson's disease (PD) is characterized by a progressive degeneration of the nigrostriatal dopaminergic pathway resulting in movement disorders. Although its etiology remains unknown, PD may be the final outcome of interactions among multiple factors, including exposure to environmental toxins and the occurrence of inflammation in the brain. In this study, using primary mesencephalic cultures, we observed that nontoxic or minimally toxic concentrations of the pesticide rotenone (0.5 nM) and the inflammogen lipopolysaccharide (LPS) (0.5 ng/ml) synergistically induced dopaminergic neurodegeneration. The synergistic neurotoxicity of rotenone and LPS was observed when the two agents were applied either simultaneously or in tandem. Mechanistically, microglial NADPH oxidase-mediated generation of reactive oxygen species appeared to be a key contributor to the synergistic dopaminergic neurotoxicity. This conclusion was based on the following observations. First, inhibition of NADPH oxidase or scavenging of free radicals afforded significant neuroprotection. Second, rotenone and LPS synergistically stimulated the NADPH oxidase-mediated release of the superoxide free radical. Third and most importantly, rotenone and LPS failed to induce the synergistic neurotoxicity as well as the production of superoxide in cultures from NADPH oxidase-deficient animals. This is the first demonstration that low concentrations of a pesticide and an inflammogen work in synergy to induce a selective degeneration of dopaminergic neurons. Findings from this study may be highly relevant to the elucidation of the multifactorial etiology of PD and the discovery of effective therapeutic agents for the treatment of the disease.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Synergistic Dopaminergic Neurotoxicity of the Pesticide Rotenone and Inflammogen Lipopolysaccharide: Relevance to the Etiology of Parkinson's Disease

et al. 2003

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“…One study reported an OR of 7.0 (p value <0.05) [289] and another an OR of 10.9 (95% CI 2.5-48.0) [301]. The remaining 19 case-control studies that analyzed results from pesticide exposure overall reported no association [131,136,137,141,142,144,145,[305][306][307][308][309][310][311][312][313][314][315][316][317].…”

Section: Case-control Studiesmentioning

confidence: 99%

“…Three case-control studies [137,141,434], one with prospective data nested within the Leisure World Cohort, California [434], reported lower risk of PD in relation to hypertension (OR 0.3, 95% CI 0.2-0.4 [141]; OR 0.48, 95% CI 0.26-0.88 [137]; OR 0.71, 95% CI 0.56-0.89 [434]). …”

Section: Vascular Diseasesmentioning

confidence: 99%

“…One case-control study reported no association for stroke, but increased PD risk associated with heart disease, although the estimate was unstable (OR 5.5, 95% CI 1.4-22.1) [358]. Another study reported decreased risk associated with ischaemic heart disease (OR 0.36, 95% CI 0.19-0.69) [137]. Yet another study reported lower risk of PD associated with previous stroke (OR 0.2, 95% CI 0.1-0.5) [141].…”

Section: Vascular Diseasesmentioning

confidence: 99%

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