Sublethal effects of waterborne uranium exposures on the zebrafish brain: transcriptional responses and alterations of the olfactory bulb ultrastructure.

The toxic action modes of uranium (U) in fish are still scarcely known. U is known to modify the acetylcholinesterase activity in the fish brain. To gain further insight into U neurotoxicity in fish, we examined transcriptional responses in the brain of the zebrafish, Danio rerio, exposed to 15 microg L(-1) and 100 microg L(-1) of waterborne U for 3 and 10 days. In parallel, an ultrastructure analysis of the neuropil of the olfactory bulb, an area in the brain of fish sensitive to metal contamination, was performed after 10 days of U exposure. This combined transcriptomic and histological study is the first report performed in the brain and specifically the olfactory bulb of fish exposed to U. We found that 56 transcripts responded to the metal exposure, and the anatomical structure of the olfactory bulb was damaged. The greatest gene response occurred at the lower U concentration and the numbers of responding genes common to any two U exposures were much smaller than those unique to each exposure. These data showed that the intensity of gene response may not correlate positively with toxicant concentrations according to our experimental design. Instead, different patterns of gene expression are expected for each exposure. Gene responses were categorized into eight functional classes, and the transcriptional responses of genes involved in the olfactory system were significantly affected. Collectively, the data suggest that genes in the olfactory region may be ecologically relevant and sensitive transcriptional biomarkers of U waterborne exposure.