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Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat.
Neurobiol Dis. 2002 Jul; 10(2):119-27.ND

Abstract

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.

Authors+Show Affiliations

The Parkinson's Institute, Sunnyvale, California 94089, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12127150

Citation

McCormack, Alison L., et al. "Environmental Risk Factors and Parkinson's Disease: Selective Degeneration of Nigral Dopaminergic Neurons Caused By the Herbicide Paraquat." Neurobiology of Disease, vol. 10, no. 2, 2002, pp. 119-27.
McCormack AL, Thiruchelvam M, Manning-Bog AB, et al. Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiol Dis. 2002;10(2):119-27.
McCormack, A. L., Thiruchelvam, M., Manning-Bog, A. B., Thiffault, C., Langston, J. W., Cory-Slechta, D. A., & Di Monte, D. A. (2002). Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. Neurobiology of Disease, 10(2), 119-27.
McCormack AL, et al. Environmental Risk Factors and Parkinson's Disease: Selective Degeneration of Nigral Dopaminergic Neurons Caused By the Herbicide Paraquat. Neurobiol Dis. 2002;10(2):119-27. PubMed PMID: 12127150.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Environmental risk factors and Parkinson's disease: selective degeneration of nigral dopaminergic neurons caused by the herbicide paraquat. AU - McCormack,Alison L, AU - Thiruchelvam,Mona, AU - Manning-Bog,Amy B, AU - Thiffault,Christine, AU - Langston,J William, AU - Cory-Slechta,Deborah A, AU - Di Monte,Donato A, PY - 2002/7/20/pubmed PY - 2002/9/7/medline PY - 2002/7/20/entrez SP - 119 EP - 27 JF - Neurobiology of disease JO - Neurobiol Dis VL - 10 IS - 2 N2 - 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. SN - 0969-9961 UR - https://www.unboundmedicine.com/medline/citation/12127150/Environmental_risk_factors_and_Parkinson's_disease:_selective_degeneration_of_nigral_dopaminergic_neurons_caused_by_the_herbicide_paraquat_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0969996102905073 DB - PRIME DP - Unbound Medicine ER -