Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat.
By A. McCormack, M. Thiruchelvam, Amy B. Manning-Boğ, C. Thiffault, J. Langston, Deborah A. Cory-Slechta, Donato A. Di Monte. Neurobiology of Disease, 2002
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Environmental toxicants and, in particular, pesticides have been implicated as risk factors in Parkinson's disease (PD). The purpose of this study was to determine if selective nigrostriatal degeneration could be reproduced by systemic exposure of mice to the widely used herbicide paraquat. Repeated intraperitoneal paraquat injections killed dopaminergic neurons in the substantia nigra (SN) pars compacta, as assessed by stereological counting of tyrosine hydroxylase (TH)-immunoreactive and Nissl-stained neurons. This cell loss was dose- and age-dependent. Several lines of evidence indicated selective vulnerability of dopaminergic neurons to paraquat. The number of GABAergic cells was not decreased in the SN pars reticulata, and counting of Nissl-stained neurons in the hippocampus did not reveal any change in paraquat-treated mice. Degenerating cell bodies were observed by silver staining, but only in the SN pars compacta, and glial response was present in the ventral mesencephalon but not in the frontal cortex and cerebellum. No significant depletion of striatal dopamine followed paraquat administration. On the other hand, enhanced dopamine synthesis was suggested by an increase in TH activity. These findings unequivocally show that selective dopaminergic degeneration, one of the pathological hallmarks of PD, is also a characteristic of paraquat neurotoxicity. The apparent discrepancy between pathological (i.e., neurodegeneration) and neurochemical (i.e., lack of significant dopamine loss) effects represents another important feature of this paraquat model and is probably a reflection of compensatory mechanisms by which neurons that survive damage are capable of restoring neurotransmitter tissue levels.
Subfields: Neurology, Plant Science, Surgery
View Paper: https://www.semanticscholar.org/paper/d0ac038052cb5017398d8d9a352ad67f667322da
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Citations in the corpus
- Α-synuclein misfolding and Parkinson's disease. (2012, background): “Several lines of evidence point to environmental exposure as a potential contributing factor in the pathogenesis of PD [216–222].”
- Association of Pesticide Exposure with Neurologic Dysfunction and Disease (2004, background): “Several studies have implicated the herbicide paraquat (Hertzman et al. 1990; Liou et al. 1997), which produces selective degeneration of neurons involved in Parkinson disease (McCormack et al. 2002).”
- Mechanism of Toxicity in Rotenone Models of Parkinson's Disease (2003, background): “Other experimental models of PD, including 6-hydroxydopamine, paraquat, and MPTP, also implicate oxidative stress in PD (Roghani and Behzadi, 2001; McCormack et al., 2002; Mollace et al., 2003).”
- Toxin-induced models of Parkinson’s disease (2005, background): “Other investigators, however, have initially failed to see any behavioral abnormality or nigrostriatal dopaminergic pathway damage in similarly treated mice,(124,125) but then(125) they also found selective nigral dopaminergic cell loss in mice injected with paraquat.(126) Aside from this bewilderin”
- Environmental pollutants as risk factors for neurodegenerative disorders: Alzheimer and Parkinson diseases (2015, background): “) increase ROS levels in the striatal homogenate, induce a dose-dependent decrease in dopaminergic neurons from the substantia nigra, a decline in striatal dopamine nerve terminal density, and a neurobehavioral syndrome characterized by reduced ambulatory activity (Brooks et al., 1999; McCormack et ”
- Selective Neuronal Vulnerability to Oxidative Stress in the Brain (2010, neutral): “RNS, including nitric oxide, nitrogen dioxide, dinitrogen trioxide and peroxynitrite, are similarly disruptive to the redox state of cells if not detoxifi ed.”
- Parkinson disease: from pathology to molecular disease mechanisms. (2013, background): “The closest has been the ability of the structurally related paraquat, a commercial weed killer, to destroy dopaminergic cells in rodents and this links nicely to the increased risk of developing PD that repeatedly emerges from epidemiological studies, although there is no association with any speci”
- Etiology and pathogenesis of Parkinson's disease (2011, background): “paraquat to destroy nigral dopaminergic neurons after systemic administration has reinforced this view.(29) The detection of increased iron levels in the substantia nigra in PD and alterations in other iron in related parameters provided a mechanism through which free-radical S C H A P I R A A N D J”
- Molecular pathophysiology of Parkinson's disease. (2005, neutral): “2002 , McCormack et al .”
- DJ-1 Is a Redox-Dependent Molecular Chaperone That Inhibits α-Synuclein Aggregate Formation (2004, background): “…cell proteins that are modified with respect to isoelectric point in response to sublethal doses of paraquat (Mitsumoto and Nakagawa 2001; Mitsumoto et al. 2001), a toxin which generates reactive oxygen species (ROS) within cells and has been associated with DN toxicity (McCormack et al. 2002).”
- Rotenone, Paraquat, and Parkinson’s Disease (2011, background): “Experimentally, paraquat produces subcellular changes associated with PD, including increased production of reactive oxygen species, alpha-synuclein aggregation, and selective nigral injury (Dinis-Oliveira et al. 2006; Kuter et al. 2010; McCormack et al. 2002).”
- Oxidative Stress in Neurodegenerative Diseases: From Molecular Mechanisms to Clinical Applications (2017, background): “PD is the second most prevalent neurodegenerative disease characterized by dopaminergic neuron loss in the substantia nigra pars compacta of the brain [7, 91, 92].”
- Parkinson's Disease Mechanisms and Models (2003, background): “MPTP was thein -synuclein immunostaining in frontal cortex (Manresponsible neurotoxic contaminant, inadvertently pro-ning-Bog et al., 2002; McCormack et al., 2002).”
- Epidemiology and etiology of Parkinson’s disease: a review of the evidence (2011, background): “Paraquat injected intraperitoneally repeatedly in mice caused dose-dependent degeneration of dopaminergic neurons in the substantia nigra, but striatal dopamine levels were normal [368].”