title: Molecular networks related to the immune system and mitochondria are targets for the pesticide dieldrin in the zebrafish (Danio rerio) central nervous system.
abstract: The objectives of this study were to determine the behavioral and molecular responses in the adult zebrafish (Danio rerio) central nervous system (CNS) following a dietary exposure to the pesticide dieldrin. Zebrafish were fed pellets spiked with 0.03, 0.15, or 1.8μg/g dieldrin for 21days. Behavioral analysis revealed no difference in exploratory behaviors or those related to anxiety. Transcriptional networks for T-cell aggregation and selection were decreased in expression suggesting an immunosuppressive effect of dieldrin, consistent with other studies investigating organochlorine pesticides. Processes related to oxidative phosphorylation were also differentially affected by dieldrin. Quantitative proteomics (iTRAQ) using a hybrid quadrupole-Orbitrap identified 226 proteins that were different following one or more doses. These proteins included ATP synthase subunits (mitochondrial) and hypoxia up-regulated protein 1 which were decreased and NADH dehydrogenases (mitochondrial) and signal recognition particle 9 which were up-regulated. Thus, proteins affected were functionally associated with the mitochondria and a protein network analysis implicated Parkinson's disease (PD) and Huntington's disease as diseases associated with altered proteins. Molecular networks related to mitochondrial dysfunction and T-cell regulation are hypothesized to underlie the association between dieldrin and PD. These data contribute to a comprehensive transcriptomic and proteomic biomarker framework for pesticide exposures and neurodegenerative diseases.
  
  
  
  Dieldrin is a persistent organochlorine pesticide that has been associated with human neurodegenerative disease such as Parkinson's disease. Dieldrin is ranked 18th on the 2015 U.S. Agency for Toxic Substances and Disease Registry and continues to be a pesticide of concern for human health. Transcriptomics and quantitative proteomics (ITRAQ) were employed to characterize the molecular networks in the central nervous system that are altered with dietary exposure to dieldrin. We found that transcriptional and protein networks related to the immune system, mitochondria, and Parkinson's disease were preferentially affected by dieldrin. The study provides new insight into the mechanisms of dieldrin neurotoxicity that may explain, in part, the association between this pesticide and increased risks to neurodegeneration. These data contribute in a significant way to developing a molecular framework for pesticide induced neurotoxicity.
authors.affiliation: Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Cowie
authors.affiliation: Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada.
authors.forename: Kathleena I
authors.initials: KI
authors.lastname: Sarty
authors.affiliation: Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada.
authors.forename: Angella
authors.initials: A
authors.lastname: Mercer
authors.affiliation: Interdisciplinary Center for Biotechnology Research, University of Florida, Gainesville, FL 32611, USA.
authors.forename: Jin
authors.initials: J
authors.lastname: Koh
authors.affiliation: Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada.
authors.forename: Karen A
authors.initials: KA
authors.lastname: Kidd
authors.affiliation: Canadian Rivers Institute and Department of Biology, University of New Brunswick, Saint John, New Brunswick E2L 4L5, Canada; Department of Physiological Sciences and Center for Environmental and Human Toxicology, University of Florida Genetics Institute, Interdisciplinary Program in Biomedical Sciences Neuroscience, College of Veterinary Medicine, University of Florida, Gainesville, FL 32611, USA. Electronic address: cmartyn@ufl.edu.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Martyniuk
mesh_terms: D000818:Animals; D002490:Central Nervous System / Q000276:immunology / Q000378:metabolism; D004026:Dieldrin / Q000633:toxicity*; D008928:Mitochondria / Q000276:immunology / Q000378:metabolism; D024101:Mitochondrial Proteins / Q000276:immunology / Q000378:metabolism; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000235:genetics / Q000276:immunology; D020258:Neurotoxicity Syndromes / Q000276:immunology / Q000378:metabolism; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000276:immunology / Q000378:metabolism; D010575:Pesticides / Q000633:toxicity*; D015027:Zebrafish / Q000276:immunology / Q000378:metabolism; D029961:Zebrafish Proteins / Q000276:immunology / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D010575:Pesticides; D029961:Zebrafish Proteins; D004026:Dieldrin
keywords: Biomarker; Immune system; Mitochondrial dysfunction; Pesticides; Proteomics; Systems biology