Mechanisms and biomarkers of cadmium induced neurobehavioral impairment in the olfactory system of coho salmon (Oncorhynchus kisutch)
Williams, Chase Rockwell
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Pacific salmon populations on the west coast of the U.S. are increasingly threatened by anthropogenic activities. One potential factor driving the population declines is disruption of olfactory function via waterborne pollutants. The salmon olfactory system is highly susceptible to disruption by waterborne pollutants such as metals. A majority of the current research has focused on the olfactory toxicity of waterborne copper, while other metals such as cadmium (Cd) have gone relatively understudied. This is a large concern as Cd is a common pollutant in many urban and agricultural waterways, some of which can be important salmon migratory routes. For my doctoral research, I focused on understanding the mechanisms underlying Cd mediated olfactory dysfunction using juvenile coho salmon parr (Oncorhynchus kisutch). The research goals for aim 1 of my project were to analyze olfactory-mediated alarm responses, epithelial injury and recovery, and a suite of olfactory molecular biomarkers encoding genes critical in maintaining olfactory function in juvenile coho salmon receiving acute exposures to Cd. The mRNA molecular biomarkers analyzed included four G-protein coupled receptors (GPCRs) representing the two major classes of odorant receptors, as well as markers of neurite outgrowth and metal/antioxidant responses to metals. Coho received acute (8-168hr) exposures to 3.7 µg/L and 347 µg/L Cd, and a subset of fish was analyzed following a 16-day depuration. Coho exposed to 347 µg/L Cd over 48hrs exhibited a reduction in freeze responses, and an extensive loss of olfaction accompanied by histological injury to the olfactory epithelium. The olfactory injury in coho exposed to 347 µg/L Cd was accompanied at the gene level by significant decreases in expression of the olfactory GPCRs and increased expression of metal and antioxidant response markers. Persistent behavioral deficits, histological injury and altered expression of a subset of olfactory biomarkers were still evident in Cd-exposed coho following a 16-day depuration in clean water. Exposure to 3.7 µg/L Cd also resulted in reduced freeze responses and histological changes to the olfactory epithelium within 48hrs of Cd exposure, although the extent of olfactory injury was less severe than observed for fish in the high Cd exposure group. Furthermore, adverse behavioral effects were present in some coho receiving the low Cd exposure following a 16-day depuration. Based on these findings, the goals for Aim 2 of my research were to investigate the toxicity of Cd on salmon olfactory function that modeled a transient sub-chronic exposure scenario. Coho were exposed to environmentally relevant concentrations of waterborne Cd (0.3, 2, and 30 µg/L) for 48hrs and 16 days, followed by a 16-day depuration. Exposures to Cd significantly and persistently altered behavioral responses towards L-cysteine and conspecific odorants. Behavioral alterations following exposure to 30 µg/L Cd were associated with increased olfactory epithelial gene expression of stress markers metallothionein and heme oxygenase, altered protein expression of olfactory signal transduction (OST) molecules critical in maintaining olfactory function, and altered gene expression of major coho odorant receptors (ORs). Exposure to Cd predominantly decreased expression of OST protein and OR molecular markers of ciliated olfactory sensory neurons (OSNs) compared to OST and OR markers of microvillus OSNs, suggesting a differential sensitivity towards Cd between the two major OSN populations. Behavioral alterations on exposure 0.3 and 2 µg/L Cd did not coincide with major histological injury or molecular changes in expression of major OST or OR markers, likely indicating disrupted signal transduction as the major mechanism underlying the olfactory behavioral dysfunction at the low-level Cd exposures. In summary, transient exposures to very low-levels of Cd can induce significant and persistent alterations of olfactory function in juvenile salmon, which could lead to increased mortality and ultimately increased stress on already threatened populations.
- Environmental health