title: Combined exposure to agriculture pesticides, paraquat and maneb, induces alterations in the N/OFQ-NOPr and PDYN/KOPr systems in rats: Relevance to sporadic Parkinson's disease.
abstract: 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-NOP and prodynorphin-KOP 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-NOP and prodynorphin-KOP systems in a chronic paraquat and maneb animal model of Parkinson's disease. Our results showed that after paraquat/maneb (5/15 mg kg(-1) ) treatment, a significant reduction in tyrosine hydroxylase (TH) levels, the rate-limiting enzyme for dopamine synthesis, was observed. Also, the association of paraquat and maneb (5/15 mg kg(-1) ) induced an increase in nociceptin/orphanin and a decrease of prodynorphin gene expression levels in the substantia nigra with a down-regulation of NOP and KOP receptors after both treatments in the substantia nigra and caudate putamen. These data further confirm that paraquat and maneb toxicity can modulate gene expression of the nociceptin/orphanin-NOP receptor and prodynorphin-KOP receptor systems in the substantia nigra and caudate putamen, offering further support to the hypothesis that chronic exposure to these agrochemicals might be implicated in the mechanisms underlying sporadic Parkinson's disease. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 656-663, 2015.
authors.affiliation: Department of Biology, Faculty of Science, University of Tarapacá, Arica, Chile.
authors.forename: Sussy
authors.initials: S
authors.lastname: Bastías-Candia
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Irnerio 48, 40126, Bologna, Italy.
authors.forename: Manuela
authors.initials: M
authors.lastname: Di Benedetto
authors.affiliation: Department of Biomedical Sciences, University of Teramo, Piazza Aldo Moro 45, 64100 Teramo, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: D'Addario
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Irnerio 48, 40126, Bologna, Italy.
authors.forename: Sanzio
authors.initials: S
authors.lastname: Candeletti
authors.affiliation: Department of Pharmacy and Biotechnology, Alma Mater Studiorum, University of Bologna, Irnerio 48, 40126, Bologna, Italy.
authors.forename: Patrizia
authors.initials: P
authors.lastname: Romualdi
mesh_terms: D000383:Agriculture; D000818:Animals; D015536:Down-Regulation; D004745:Enkephalins / Q000378:metabolism; D005659:Fungicides, Industrial / Q000633:toxicity*; D015870:Gene Expression / Q000187:drug effects; D006540:Herbicides / Q000633:toxicity*; D008297:Male; D008344:Maneb / Q000633:toxicity*; D018847:Opioid Peptides / Q000378:metabolism; D010269:Paraquat / Q000633:toxicity*; D010302:Parkinson Disease, Secondary / Q000139:chemically induced*; D011498:Protein Precursors / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000187:drug effects / Q000378:metabolism; D013378:Substantia Nigra; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D004745:Enkephalins; D005659:Fungicides, Industrial; D006540:Herbicides; D008344:Maneb; D018847:Opioid Peptides; D010269:Paraquat; D011498:Protein Precursors; D011957:Receptors, Opioid; D014446:Tyrosine 3-Monooxygenase; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C033660:preproenkephalin; C000722285:Oprl1 protein, rat
keywords: N/OFQ-NOPr system; PDYN-KOPr system; Parkinson's disease; pesticides