title: Mancozeb-induced behavioral deficits precede structural neural degeneration.
abstract: Manganese-containing fungicides like Mancozeb have been associated with neurodegenerative conditions like Parkinson's disease. We examined the behavioral damage and differential neuronal vulnerability resulting from Mancozeb exposure using Caenorhabditis elegans, an important mid-trophic level soil organism that is also a powerful model for studying mechanisms of environmental pollutant-induced neurodegenerative disease. The dopamine-mediated swim to crawl locomotory transition behavior is exquisitely vulnerable to Mancozeb, with functional impairment preceding markers of neuronal structural damage. The damage is partially rescued in mutants lacking the divalent metal transporter, SMF-1, demonstrating that some, but not all, of the damage is mediated by manganese. Increasing concentrations of Mancozeb recruit additional behavioral dysfunction, notably serotonin-mediated egg-laying behavior, but without evident serotonergic neuronal structural damage. Thus, measurements of behavioral dysfunction are a sensitive early marker of fungicide toxicity that could be exploited to examine further mechanisms of neuron damage and possible therapeutic interventions. These results also provide important insight into the consequences of fungicide use on the ecological behavior of nematodes.
authors.affiliation: Program in Neuroscience and Behavior, Poughkeepsie, NY, USA. albrody@vassar.edu
authors.forename: A
authors.initials: A
authors.lastname: Harrison Brody
authors.forename: Eunice
authors.initials: E
authors.lastname: Chou
authors.forename: Janet M
authors.initials: JM
authors.lastname: Gray
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Pokyrwka
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Raley-Susman
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism; D004298:Dopamine / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004785:Environmental Pollutants / Q000378:metabolism / Q000633:toxicity*; D005659:Fungicides, Industrial / Q000378:metabolism / Q000633:toxicity*; D008124:Locomotion / Q000187:drug effects; D008344:Maneb / Q000378:metabolism / Q000633:toxicity*; D040542:Mechanotransduction, Cellular / Q000187:drug effects; D009154:Mutation; D009410:Nerve Degeneration; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D010058:Oviposition / Q000187:drug effects; D012701:Serotonin / Q000378:metabolism; D014110:Touch; D015038:Zineb / Q000378:metabolism / Q000633:toxicity*
chemical_list: D029742:Caenorhabditis elegans Proteins; D027682:Cation Transport Proteins; D004785:Environmental Pollutants; D005659:Fungicides, Industrial; C548880:smf-1 protein, C elegans; D008344:Maneb; D012701:Serotonin; C013099:mancozeb; D004298:Dopamine; D015038:Zineb