{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T08:37:26Z","timestamp":1789720646331,"version":"4.0.1"},"reference-count":37,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2013,12,23]],"date-time":"2013-12-23T00:00:00Z","timestamp":1387756800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"RFO","award":["RFO09"],"award-info":[{"award-number":["RFO09"]}]},{"name":"PRIN","award":["PRIN06"],"award-info":[{"award-number":["PRIN06"]}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Environmental Toxicology"],"published-print":{"date-parts":[[2015,5,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>Despite several years of research, the aetiology of Parkinson's disease (PD) is quite far from being solved. In PD, as well as in other neurodegenerative disorders, it has been proposed that the combination of multiple factors might contribute to the onset of the disease. Indeed, several authors have suggested that environmental factors, such as pollutants and chemicals, might be associated with the onset of several neurodegenerative disorders. On the other hand, several studies have described that the nociceptin\/orphanin\u2010NOP and prodynorphin\u2010KOP opioid systems are implicated in the pathology of Parkinson's disease. Considering the nonrestricted commercial availability and common use of several pesticides, such as paraquat and maneb, in agriculture of less developed countries, the aim of our study was to investigate the involvement of nociceptin\/orphanin\u2010NOP and prodynorphin\u2010KOP systems in a chronic paraquat and maneb animal model of Parkinson's disease. Our results showed that after paraquat\/maneb (5\/15 mg kg<jats:sup>\u22121<\/jats:sup>) treatment, a significant reduction in tyrosine hydroxylase (TH) levels, the rate\u2010limiting enzyme for dopamine synthesis, was observed. Also, the association of paraquat and maneb (5\/15 mg kg<jats:sup>\u22121<\/jats:sup>) induced an increase in nociceptin\/orphanin and a decrease of prodynorphin gene expression levels in the<jats:italic>substantia nigra<\/jats:italic>with a down\u2010regulation of NOP and KOP receptors after both treatments in the<jats:italic>substantia nigra<\/jats:italic>and<jats:italic>caudate putamen<\/jats:italic>. These data further confirm that paraquat and maneb toxicity can modulate gene expression of the nociceptin\/orphanin\u2010NOP receptor and prodynorphin\u2010KOP receptor systems in the<jats:italic>substantia nigra<\/jats:italic>and<jats:italic>caudate putamen<\/jats:italic>, offering further support to the hypothesis that chronic exposure to these agrochemicals might be implicated in the mechanisms underlying sporadic Parkinson's disease. \u00a9 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 656\u2013663, 2015.<\/jats:p>","DOI":"10.1002\/tox.21943","type":"journal-article","created":{"date-parts":[[2013,12,24]],"date-time":"2013-12-24T04:52:50Z","timestamp":1387860770000},"page":"656-663","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Combined exposure to agriculture pesticides, paraquat and maneb, induces alterations in the N\/OFQ\u2014NOPr and PDYN\/KOPr systems in rats: Relevance to sporadic Parkinson's disease"],"prefix":"10.1002","volume":"30","author":[{"given":"Sussy","family":"Bast\u00edas\u2010Candia","sequence":"first","affiliation":[{"name":"Department of Biology, Faculty of Science University of Tarapac\u00e1 Arica Chile"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Manuela","family":"Di Benedetto","sequence":"additional","affiliation":[{"name":"Department of Pharmacy and Biotechnology, Alma Mater Studiorum University of Bologna Irnerio 48 40126 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