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

Blechinger, S.R., Kusch, R.C., Haugo, K., Matz, C., Chivers, D.P., and Krone, P.H.
Toxicology and applied pharmacology   224(1): 72-80 (Journal)
Registered Authors
Krone, Patrick H.
Olfactory epithelium, Zebrafish larvae, Cadmium, Alarm substance, Cell death, Lateral line
MeSH Terms
  • Animals
  • Behavior, Animal/drug effects
  • Cadmium/toxicity*
  • Cell Death/drug effects*
  • Embryo, Nonmammalian/physiology*
  • Endpoint Determination
  • 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
  • Larva/physiology
  • Lateral Line System/pathology
  • Neurons, Afferent/drug effects
  • Neurons, Afferent/metabolism
  • Olfaction Disorders/chemically induced*
  • Olfaction Disorders/psychology
  • Olfactory Mucosa/pathology
  • Predatory Behavior/drug effects
  • Smell/drug effects*
  • Stress, Physiological/pathology*
  • Up-Regulation/drug effects
  • Water Pollutants, Chemical/toxicity
  • Zebrafish
17706735 Full text @ Tox. App. Pharmacol.
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.
Genes / Markers
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Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Engineered Foreign Genes