Pacific salmon populations have declined markedly in the Western United States. Of particular concern has been sublethal neurological injury occurring in salmon exposed to certain pesticides and trace metals. These behavioral impacts include loss of predator detection and prey selection, altered reproductive timing and loss of homing. These aforementioned neurobehavioral effects observed in individuals are now linked to population impacts. The salmon olfactory system is a sensitive target for the neurotoxicity of environmental chemicals, including metals and pesticides commonly found in Superfund sites. However, little is known about the mechanisms of chemical olfactory neurotoxicity in fish. Studies from our first funding cycle have produced important findings that will be explored in detail in our competitive renewal. Specifically, we know that: 1) the olfactory tissues of salmon are important site of chemical biotransformation, and in particular, cytochrome P4503A and flavin monooxygenases (FMO) appear to mediate tissue- and compound-specific differences in organophosphate biotransformation with potential impacts on neurotoxicity, 2) the olfactory injury by a model superfund organophosphate chemical (chlorpyrifos) and metal (copper) involves disruption of olfactory signal transduction pathways. However, copper primarily impacts G-protein coupled olfactory receptor signaling, likely through oxidative stress, whereas chlorpyrifos activates genes involved in the inhibition of olfactory signal transduction, and 3) transcriptional signatures can help us identify unique gene targets relevant to mixtures, as well differentiating metal- and organophosphate-driven affects. Based upon our findings, the objectives of the competing renewal are to: 1) use cDNA cloning, recombinant protein expression, microarray analysis and enzymatic approaches to determine the role of olfactory CYP3A and flavin monooxygenases in organophosphate neurotoxicity in salmon during movement from freshwater to saltwater, 2) use in situ hybridization and immunohistochemistry analyses coupled with behavioral studies to understand the role of oxidative stress in copper and cadmium-mediated olfactory injury, 3) use proteomics approaches to identify and discriminate important olfactory protein targets of copper and chlorpyrifos, 4) use a suite of olfactory biomarkers generated from the aforementioned studies to assess sublethal olfactory neurotoxicity in salmon migrating through Superfund sites.
The results this project will greatly increase our understanding of the mechanisms and consequences of sublethal neurotoxicity in salmon populations, and will use mechanistically-based biomarkers to identify salmon undergoing behavioral injuries as a consequence of chemical exposures at Superfund sites. Furthermore, this study has global implications for the consequences of aquatic pollution to freshwater and marine fish, which rely heavily upon proper olfactory functioning for the maintenance of normal behaviors critical to survival and reproduction.
|Marsillach, Judit; Suzuki, Stephanie M; Richter, Rebecca J et al. (2014) Human valacyclovir hydrolase/biphenyl hydrolase-like protein is a highly efficient homocysteine thiolactonase. PLoS One 9:e110054|
|Lundin, Jessica I; Checkoway, Harvey; Criswell, Susan R et al. (2014) Screening for early detection of parkinsonism using a self-administered questionnaire: a cross-sectional epidemiologic study. Neurotoxicology 45:232-7|
|Racette, Brad A (2014) Manganism in the 21st century: the Hanninen lecture. Neurotoxicology 45:201-7|
|Kang, Jun Won; Doty, Sharon Lafferty (2014) Cometabolic degradation of trichloroethylene by Burkholderia cepacia G4 with poplar leaf homogenate. Can J Microbiol 60:487-90|
|Costa, Lucio G; de Laat, Rian; Tagliaferri, Sara et al. (2014) A mechanistic view of polybrominated diphenyl ether (PBDE) developmental neurotoxicity. Toxicol Lett 230:282-94|
|Maryoung, Lindley A; Lavado, Ramon; Schlenk, Daniel (2014) Impacts of hypersaline acclimation on the acute toxicity of the organophosphate chlorpyrifos to salmonids. Aquat Toxicol 152:284-90|
|Cole, Toby B; Li, Wan-Fen; Co, Aila L et al. (2014) Repeated gestational exposure of mice to chlorpyrifos oxon is associated with paraoxonase 1 (PON1) modulated effects in maternal and fetal tissues. Toxicol Sci 141:409-22|
|Woods, James S; Heyer, Nicholas J; Russo, Joan E et al. (2014) Genetic polymorphisms affecting susceptibility to mercury neurotoxicity in children: summary findings from the Casa Pia Children's Amalgam clinical trial. Neurotoxicology 44:288-302|
|Woods, James S; Heyer, Nicholas J; Russo, Joan E et al. (2014) Genetic polymorphisms of catechol-O-methyltransferase modify the neurobehavioral effects of mercury in children. J Toxicol Environ Health A 77:293-312|
|Stewart, Tessandra; Sui, Yu-Ting; Gonzalez-Cuyar, Luis F et al. (2014) Cheek cell-derived *-synuclein and DJ-1 do not differentiate Parkinson's disease from control. Neurobiol Aging 35:418-20|
Showing the most recent 10 out of 381 publications