title: Brief embryonic cadmium exposure induces a stress response and cell death in the developing olfactory system followed by long-term olfactory deficits in juvenile zebrafish.
abstract: The toxic effects of cadmium and other metals have been well established. A primary target of these metals is known to be the olfactory system, and fish exposed to a number of different waterborne metals display deficiencies in olfaction. Importantly, exposure over embryonic/larval development periods can cause deficits in chemosensory function in juvenile fish, but the specific cell types affected are unknown. We have previously characterized a transgenic zebrafish strain expressing the green fluorescent protein (eGFP) gene linked to the hsp70 gene promoter, and shown it to be a useful tool for examining cell-specific toxicity in living embryos and larvae. Here we show that the hsp70/eGFP transgene is strongly and specifically upregulated within the olfactory sensory neurons (OSNs) of transgenic zebrafish larvae following a brief 3-h exposure to water-borne cadmium. This molecular response was closely correlated to an endpoint for tissue damage within the olfactory placode, namely cell death. Furthermore, cadmium-induced olfactory cytotoxicity in zebrafish larvae gives rise to more permanent effects. Juvenile zebrafish briefly exposed to cadmium during early larval development display deficits in olfactory-dependent predator avoidance behaviors 4-6 weeks after a return to clean water. Lateral line neuromasts of exposed zebrafish larvae also activate both the endogenous hsp70 gene and the hsp70/eGFP transgene. The data reveal that even a very brief exposure period that gives rise to cell death within the developing olfactory placode results in long-term deficits in olfaction, and that hsp70/eGFP may serve as an effective indicator of sublethal cadmium exposure in sensory cells.
authors: Department of Anatomy and Cell Biology, University of Saskatchewan, Saskatoon, Saskatchewan, Canada.
authors: Scott R
authors: SR
authors: Blechinger
authors: Robin C
authors: RC
authors: Kusch
authors: Kristine
authors: K
authors: Haugo
authors: Carlyn
authors: C
authors: Matz
authors: Douglas P
authors: DP
authors: Chivers
authors: Patrick H
authors: PH
authors: Krone
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002104:Cadmium / Q000633:toxicity*; D016923:Cell Death / Q000187:drug effects*; D004625:Embryo, Nonmammalian / Q000502:physiology*; D023381:Endpoint Determination; D018840:HSP70 Heat-Shock Proteins / Q000096:biosynthesis / Q000235:genetics; D007091:Image Processing, Computer-Assisted; D017403:In Situ Hybridization; D020287:In Situ Nick-End Labeling; D007202:Indicators and Reagents; D007814:Larva / Q000502:physiology; D053403:Lateral Line System / Q000473:pathology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism; D000857:Olfaction Disorders / Q000139:chemically induced* / Q000523:psychology; D009831:Olfactory Mucosa / Q000473:pathology; D011235:Predatory Behavior / Q000187:drug effects; D012903:Smell / Q000187:drug effects*; D013312:Stress, Physiological / Q000473:pathology*; D015854:Up-Regulation / Q000187:drug effects; D014874:Water Pollutants, Chemical / Q000633:toxicity; D015027:Zebrafish
chemical_list: D018840:HSP70 Heat-Shock Proteins; D007202:Indicators and Reagents; D014874:Water Pollutants, Chemical; D002104:Cadmium