Differential influences of (±) anatoxin-a on photolocomotor behavior and gene transcription in larval zebrafish and fathead minnows

BACKGROUND: Though anatoxin-a (antx-a) is a globally important cyanobacterial neurotoxin in inland waters, information on sublethal toxicological responses of aquatic organisms is limited. We examined influences of (±) antx-a (11–3490 μg/L) on photolocomotor behavioral responses and gene transcription associated with neurotoxicity, oxidative stress and hepatotoxicity, in two of the most common alternative vertebrate and fish models, Danio rerio (zebrafish) and Pimephales promelas (fathead minnow). We selected environmentally relevant treatment levels from probabilistic exposure distributions, employed standardized experimental designs, and analytically verified treatment levels using isotope-dilution liquid chromatography tandem mass spectrometry. Caffeine was examined as a positive control. RESULTS: Caffeine influences on fish behavior responses were similar to previous studies. Following exposure to (±) antx-a, no significant photolocomotor effects were observed during light and dark transitions for either species. Though zebrafish behavioral responses profiles were not significantly affected by (±) antx-a at the environmentally relevant treatment levels examined, fathead minnow stimulatory behavior was significantly reduced in the 145–1960 μg/L treatment levels. In addition, no significant changes in transcription of target genes were observed in zebrafish; however, elavl3 and sod1 were upregulated and gst and cyp3a126 were significantly downregulated in fathead minnows. CONCLUSION: We observed differential influences of (±) antx-a on swimming behavior and gene transcription in two of the most common larval fish models employed for prospective and retrospective assessment of environmental contaminants and water quality conditions. Sublethal responses of fathead minnows were consistently more sensitive than zebrafish to this neurotoxin at the environmentally relevant concentrations examined. Future studies are needed to understand such interspecies differences, the enantioselective toxicity of this compound, molecular initiation events within adverse outcome pathways, and subsequent individual and population risks for this emerging water quality threat.