Developmental pesticide exposures and the Parkinson's disease phenotype.
Whereas Parkinson's disease is a neurodegenerative disorder that typically onsets after 60 years of age, the possibility that it could result from insults sustained during development has been proposed. Experimental evidence based on the combined paraquat + maneb model of the Parkinson's disease (PD) phenotype summarized here provides support for such an assertion. Postnatal exposures of mice to these pesticides led not only to a permanent and selective loss of dopaminergic neurons in the substantia nigra pars compacta but also enhanced the impact of these pesticides administered during adulthood relative to developmental only or adult only treatment. Exposure to maneb alone during gestation resulted in a dramatic response to paraquat in adulthood, including notable reductions in levels of dopamine and metabolites and a loss of nigral dopamine (DA) neurons, despite the fact that paraquat does not share structural similarity to or mechanisms of action with maneb. Collectively, these studies provide developmental environmental models of the PD phenotype. In addition, they demonstrate the fact that silent neurotoxicity produced by developmental insults can be unmasked by challenges later during life as well as the potential for cumulative neurotoxicity over the life span.
Cory-Slechta
Deborah A
DA
Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 170 Frelinghuysen Road, Piscataway, NJ 08854, USA. dcs@eohsi.rutgers.edu
Thiruchelvam
Mona
M
Richfield
Eric K
EK
Barlow
Brian K
BK
Brooks
Andrew I
AI
D000367:Age Factors; D000818:Animals; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D005260:Female; D018698:Glutamic Acid / Q000378:metabolism; D006801:Humans; D051379:Mice; D010300:Parkinson Disease / Q000151:congenital / Q000209:etiology*; D010575:Pesticides / Q000009:adverse effects*; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects
D010575:Pesticides; D018698:Glutamic Acid; D004298:Dopamine