Effects of diazepam on gene expression and link to physiological effects in different life stages in zebrafish Danio rerio.
We applied zebrafish whole genome microarrays to identify molecular effects of diazepam, a neuropharmaceutical encountered in wastewater-contaminated environments, and to elucidate its neurotoxic mode of action. Behavioral studies were performed to analyze for correlations between altered gene expression with effects on the organism level. Male zebrafish and zebrafish eleuthero-embryos were exposed for 14 d or up to 3 d after hatching, respectively, to nominal levels of 273 ng/L and 273 μg/L (determined water concentrations in the adult experiment 235 ng/L and 291 μg/L). Among the 51 and 103 altered transcripts at both concentrations, respectively, the expression of genes involved in the circadian rhythm in adult zebrafish and eleuthero-embryos were of particular significance, as revealed both by microarrays and quantitative PCR. The swimming behavior of eleuthero-embryos was significantly altered at 273 μg/L. The study leads to the conclusion that diazepam-induced alterations of genes involved in circadian rhythm are paralleled by effects in neurobehavior at high, but not at low diazepam concentrations that may occur in polluted environments.
Oggier
Daniela M
DM
School of Life Sciences, University of Applied Sciences Northwestern Switzerland, Gründenstrasse 40, CH-4132 Muttenz, Switzerland.
Weisbrod
Christin J
CJ
Stoller
Andrea M
AM
Zenker
Armin K
AK
Fent
Karl
K
D000818:Animals; D002940:Circadian Rhythm; D003975:Diazepam / Q000494:pharmacology*; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D008018:Life Cycle Stages; D008297:Male; D009693:Nucleic Acid Hybridization; D012313:RNA / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015027:Zebrafish / Q000235:genetics / Q000254:growth & development* / Q000502:physiology
D012313:RNA; D003975:Diazepam