Effects of Single and Combined Low Concentrations of Neuroactive Drugs on Daphnia magna Reproduction and Transcriptomic Responses

Assessing
the risk of neuroactive pharmaceuticals in the environment
requires an understanding of their joint effects at low concentrations
across species. Here, we assessed reproductive and transcriptional
effects of single and ternary equi-effective mixture exposure to propranolol,
diazepam, and carbamazepine on the crustacean Daphnia
magna at environmentally relevant concentrations.
The three compounds enhanced reproduction in adults and induced specific
transcriptome changes in preadolescent individuals. Comparison of
the results from single exposures to a ternary equi-effective mixture
of the three compounds showed additive action. Transcriptomic analyses
identified 3248 genes affected by at least one of the treatments,
which were grouped into four clusters. Two clusters (1897 gene transcripts
in total) behaved similarly, appearing either over- or under-represented
relative to control, in all single and mixture treatments. The third
and fourth clusters grouped genes differently transcribed upon exposure
to diazepam and propranolol, respectively. Functional transcriptomics
analysis indicated that the four clusters shared major deregulated
signaling pathways implicated on energy, growth, reproduction, and
neurologically related processes, which may be responsible for the
observed reproductive effects. Thus, our study showed additive effects
at the transcriptional and physiological level and provides a novel
approach to the analysis of environmentally relevant mixtures of neuroactive
compounds.