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

• Published in: Toxicology and applied pharmacology Vol. 224; no. 1; pp. 72 - 80
• Main Authors: Blechinger, Scott R., Kusch, Robin C., Haugo, Kristine, Matz, Carlyn, Chivers, Douglas P., Krone, Patrick H.
• Format: Journal Article
• Language: English
• Published: San Diego, CA Elsevier Inc 01.10.2007; Elsevier
• Subjects: 60 APPLIED LIFE SCIENCES; Alarm substance; Animals; APOPTOSIS; Behavior, Animal - drug effects; Biological and medical sciences; BIOLOGICAL INDICATORS; BIOLOGICAL STRESS; CADMIUM; Cadmium - toxicity; Cell death; Cell Death - drug effects; Chemical and industrial products toxicology. Toxic occupational diseases; Danio rerio; Embryo, Nonmammalian - physiology; Endpoint Determination; EPITHELIUM; GENES; HSP70 Heat-Shock Proteins - biosynthesis; HSP70 Heat-Shock Proteins - genetics; Image Processing, Computer-Assisted; In Situ Hybridization; In Situ Nick-End Labeling; Indicators and Reagents; JUVENILES; Larva - physiology; LARVAE; Lateral line; Lateral Line System - pathology; Medical sciences; Metals and various inorganic compounds; NERVE CELLS; Neurons, Afferent - drug effects; Neurons, Afferent - metabolism; Olfaction Disorders - chemically induced; Olfaction Disorders - psychology; Olfactory epithelium; Olfactory Mucosa - pathology; Predatory Behavior - drug effects; Smell - drug effects; Stress, Physiological - pathology; TOXICITY; Toxicology; Up-Regulation - drug effects; Water Pollutants, Chemical - toxicity; Zebrafish; Zebrafish larvae; Zebrafish larvae; Cadmium; Lateral line; Olfactory epithelium; Cell death; Alarm substance; Embryo; Exposure; Long term; Olfactory system; Stress; Heavy metal; Vertebrata; Brachydanio rerio; Larva; Pisces; Alarm; Olfaction; Apoptosis
• ISSN: 0041-008X; 1096-0333
• DOI: 10.1016/j.taap.2007.06.025

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.