Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss

Brooks, Andrew I.; Chadwick, Chris; Gelbard, Harris A.; Cory‐Slechta, Deborah A.; Federoff, Howard J.

doi:10.1016/s0006-8993(98)01192-5

Cited by 367 publications

(235 citation statements)

References 43 publications

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“…Furthermore, overexpression of either wild-type or mutant α-synuclein is protective against paraquat toxicity [34]. Others report that paraquat causes loss of nigral dopamine neurons and degeneration of striatal terminals, as well as decreased locomotor activity [35,36]. These studies support the ability of paraquat exposure to result in a reproducible loss of dopamine neurons.…”

Section: Paraquatmentioning

confidence: 73%

Parkinson's disease and pesticides: a toxicological perspective

Hatcher

Pennell

Miller

2008

Trends in Pharmacological Sciences

288

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: Paraquatmentioning

confidence: 73%

Parkinson's disease and pesticides: a toxicological perspective

Hatcher

Pennell

Miller

2008

Trends in Pharmacological Sciences

288

176

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“…) and is a widely used herbicide that has very recently been associated with human PD (odds ratio = 2.5, 95% confidence interval 1.4, 4.7) (102). PQ treatment elicits a selective and dose-dependent loss of nigral DA neurons with associated modest decreases in striatal dopamine nerve terminal density and mildly decreased motor behavior (9,64). Following sustained systemic intraperitoneal administration, PQ was found to have a very long half-life in the mouse brain (up to 28 days) and was associated with ongoing lipid peroxidation (77).…”

Section: Paraquat and Maneb Models Of Parkinsonismmentioning

confidence: 99%

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

Martinez

Greenamyre

2012

Antioxidants & Redox Signaling

217

155

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Significance: Parkinson's disease (PD) is a neurodegenerative disorder characterized, in part, by the progressive and selective loss of dopaminergic neuron cell bodies within the substantia nigra pars compacta (SNpc) and the associated deficiency of the neurotransmitter dopamine (DA) in the striatum, which gives rise to the typical motor symptoms of PD. The mechanisms that contribute to the induction and progressive cell death of dopaminergic neurons in PD are multi-faceted and remain incompletely understood. Data from epidemiological studies in humans and molecular studies in genetic, as well as toxin-induced animal models of parkinsonism, indicate that mitochondrial dysfunction occurs early in the pathogenesis of both familial and idiopathic PD. In this review, we provide an overview of toxin models of mitochondrial dysfunction in experimental Parkinson's disease and discuss mitochondrial mechanisms of neurotoxicity. Recent Advances: A new toxin model using the mitochondrial toxin trichloroethylene was recently described and novel methods, such as intranasal exposure to toxins, have been explored. Additionally, recent research conducted in toxin models of parkinsonism provides an emerging emphasis on extranigral aspects of PD pathology. Critical Issues: Unfortunately, none of the existing animal models of experimental PD completely mimics the etiology, progression, and pathology of human PD. Future Directions: Continued efforts to optimize established animal models of parkinsonism, as well as the development and characterization of new animal models are essential, as there still remains a disconnect in terms of translating mechanistic observations in animal models of experimental PD into bona fide diseasemodifying therapeutics for human PD patients. Antioxid. Redox Signal. 16, 920-934.

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“…Subsequent studies showing that certain pesticides (Sanchez-Ramos et al 1998;Betarbet et al 2000) or herbicides (Brooks et al 1999) also capable of inhibiting complex I can produce animal models for PD have provided support for the environmental hypothesis for PD. Further studies using human tissues have shown that complex I activity is decreased in the platelets (\50%) of PD subjects (Parker et al 1989) and in substantia nigra (30-40%) obtained at autopsy from PD patients (Schapira et al 1990).…”

Section: Introductionmentioning

confidence: 98%

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

et al. 2008

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Mitochondrial complex I deficiency has been implicated in the pathogenesis of Parkinson's disease (PD), but as yet no mitochondrial DNA (mtDNA) variations have been identified that could account for the impaired complex I activity. On the other hand, it has been suggested that mtDNA polymorphisms (mtSNPs) or haplogroups may modify the risk of developing PD. Here, we determined the distributions of ten mtSNPs that define the nine major European haplogroups among 224 PD patients and 383 controls from Crete, an island of 0.6 million inhabitants who share a similar genetic background and a common environment. The recruitment of patients and controls was restricted to individuals of Cretan origin for at least three generations from both parental sides in order to avoid population admixture and subsequent genetic heterogeneity. We found no mtSNP or mtDNA haplogroup that predisposes to PD, although there was a trend for haplogroups J, T, U and I and the supercluster of haplogroups UKJT to be slightly underrepresented in our PD patients as compared to controls. While a combination of common mtSNPs (present in C5% of the general population) may decrease the chance of developing PD, this effect was minor in the Cretan population.

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Paraquat elicited neurobehavioral syndrome caused by dopaminergic neuron loss

Cited by 367 publications

References 43 publications

Parkinson's disease and pesticides: a toxicological perspective

Parkinson's disease and pesticides: a toxicological perspective

Toxin Models of Mitochondrial Dysfunction in Parkinson's Disease

Mitochondrial DNA polymorphisms and haplogroups in Parkinson’s disease and control individuals with a similar genetic background

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