{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:02:45Z","timestamp":1790625765410,"version":"4.1.0"},"reference-count":58,"publisher":"American Chemical Society (ACS)","issue":"9","license":[{"start":{"date-parts":[[2017,12,29]],"date-time":"2017-12-29T00:00:00Z","timestamp":1514505600000},"content-version":"vor","delay-in-days":4600,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2005,9,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>It has been hypothesized that developmental insults could contribute to Parkinson disease (PD), a neurodegenerative disorder resulting from the loss of the dopamine neurons of the nigrostriatal pathway. Two models of developmental pesticide exposures in mice are presented here that yield PD phenotypes consistent with this possibility. Combined exposures to the herbicide paraquat (PQ) and the fungicide maneb (MB), both of which adversely affect dopamine systems, administered from postnatal days 5\u201319, produced selective losses of dopamine and metabolites and reduced numbers of dopamine neurons in the substantia nigra. Effects were greater than those produced by adult-only exposures. Moreover, developmental PQ + MB exposures enhanced vulnerability to this pesticide regimen when administered subsequently in adulthood. In a second model, exposure to MB from gestational days 10\u201317 markedly increased vulnerability to PQ exposures during adulthood, with reductions in dopamine and metabolites and numbers of dopamine neurons in the substantia nigra. Females evidenced protection in both models. Collectively, these models demonstrate that developmental exposures can produce progressive, permanent, and cumulative neurotoxicity of the nigrostriatal dopamine system and enhance vulnerability to subsequent environmental insults. Finally, effects of PQ + MB were greater than those of either pesticide alone in the postnatal model. This is consistent with a multiple-hit hypothesis predicting that multiple concurrent insults occurring at different target sites within a system (here nigrostriatal dopamine) may constrict the range and flexibility of compensatory mechanisms, thereby compromising the integrity and viability of the system. As such, this hypothesis presents a biologic strategy for identifying potentially significant neurotoxic mixtures for hazard identification in future studies.<\/jats:p>","DOI":"10.1289\/ehp.7570","type":"journal-article","created":{"date-parts":[[2005,5,26]],"date-time":"2005-05-26T16:53:38Z","timestamp":1117126418000},"page":"1263-1270","source":"Crossref","is-referenced-by-count":111,"title":["Developmental Pesticide Models of the Parkinson Disease Phenotype"],"prefix":"10.1021","volume":"113","author":[{"given":"Deborah A.","family":"Cory-Slechta","sequence":"first","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey and Rutgers University, Piscataway, New Jersey, USA"},{"name":"Department of Environmental and Occupational Medicine, and"},{"name":"Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, University of Medicine and Dentistry of New Jersey, Piscataway, New Jersey, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mona","family":"Thiruchelvam","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey and Rutgers University, Piscataway, New Jersey, USA"},{"name":"Department of Environmental and Occupational Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian K.","family":"Barlow","sequence":"additional","affiliation":[{"name":"Department of Environmental and Occupational Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric K.","family":"Richfield","sequence":"additional","affiliation":[{"name":"Environmental and Occupational Health Sciences Institute, University of Medicine and Dentistry of New Jersey and Rutgers University, Piscataway, New Jersey, USA"},{"name":"Department of Pathology and Laboratory Medicine, Robert Wood Johnson Medical School, University of 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