Depressing Antidepressant: Fluoxetine Affects Serotonin Neurons Causing Adverse Reproductive Responses in Daphnia magna

Selective serotonin reuptake inhibitors (SSRIs) are widely used antidepressants. As endocrine disruptive contaminants in the environment, SSRIs affect reproduction in aquatic organisms. In the water flea Daphnia magna, SSRIs increase offspring production in a food ration-dependent manner. At limiting food conditions, females exposed to SSRIs produce more but smaller offspring, which is a maladaptive life-history strategy. We asked whether increased serotonin levels in newly identified serotonin-neurons in the Daphnia brain mediate these effects. We provide strong evidence that exogenous SSRI fluoxetine selectively increases serotonin-immunoreactivity in identified brain neurons under limiting food conditions thereby leading to maladaptive offspring production. Fluoxetine increases serotonin-immuno­reactivity at low food conditions to similar maximal levels as observed under high food conditions and concomitantly enhances offspring production. Sublethal amounts of the neurotoxin 5,7-dihydroxytryptamine known to specifically ablate serotonin-neurons markedly decrease serotonin-immunoreactivity and offspring production, strongly supporting the effect to be serotonin-specific by reversing the reproductive phenotype attained under fluoxetine. Thus, SSRIs impair serotonin-regulation of reproductive investment in a planktonic key organism causing inappropriately increased reproduction with potentially severe ecological impact

Bacteria-Mediated Effects of Antibiotics on <i>Daphnia</i> Nutrition

In polluted environments, contaminant effects may be manifested via both direct toxicity to the host and changes in its microbiota, affecting bacteria–host interactions. In this context, particularly relevant is exposure to antibiotics released into environment. We examined effects of the antibiotic trimethoprim on microbiota of Daphnia magna and concomitant changes in the host feeding. In daphnids exposed to 0.25 mg L^–1 trimethoprim for 24 h, the microbiota was strongly affected, with (1) up to 21-fold decrease in 16S rRNA gene abundance and (2) a shift from balanced communities dominated by <i>Curvibacter</i>, <i>Aquabacterium,</i> and <i>Limnohabitans</i> in controls to significantly lower diversity under dominance of <i>Pelomonas</i> in the exposed animals. Moreover, decreased feeding and digestion was observed in the animals exposed to 0.25–2 mg L^–1 trimethoprim for 48 h and then fed ¹⁴C-labeled algae. Whereas the proportion of intact algal cells in the guts increased with increased trimethoprim concentration, ingestion and incorporation rates as well as digestion and incorporation efficiencies decreased significantly. Thus, antibiotics may impact nontarget species via changes in their microbiota leading to compromised nutrition and, ultimately, growth. These bacteria-mediated effects in nontarget organisms may not be unique for antibiotics, but also relevant for environmental pollutants of various nature

Identification of Metabolic Pathways in <i>Daphnia magna</i> Explaining Hormetic Effects of Selective Serotonin Reuptake Inhibitors and 4‑Nonylphenol Using Transcriptomic and Phenotypic Responses

The molecular mechanisms explaining hormetic effects of selective serotonin reuptake inhibitors (SSRIs) and 4-nonylphenol in <i>Daphnia magna</i> reproduction were studied in juveniles and adults. Transcriptome analyses showed changes in mRNA levels for 1796 genes in juveniles and 1214 genes in adults (out of 15 000 total probes) exposed to two SSRIs (fluoxetine and fluvoxamine) or to 4-nonylphenol. Functional annotation of affected genes was improved by assuming the annotations of putatively homologous <i>Drosophila</i> genes. Self-organizing map analysis and partial least-square regression coupled with selectivity ratio procedures analyses allowed to define groups of genes with specific responses to the different treatments. Differentially expressed genes were analyzed for functional enrichment using Gene Ontology and Kyoto Encyclopaedia of Genes and Genomes databases. Serotonin metabolism, neuronal developmental processes, and carbohydrates and lipid metabolism functional categories appeared as selectively affected by SSRI treatment, whereas 4-nonylphenol deregulated genes from the carbohydrate metabolism and the ecdysone regulatory pathway. These changes in functional and metabolic pathways are consistent with previously reported SSRIs and 4-nonylphenol hormetic effects in <i>D. magna</i>, including a decrease in reserve carbohydrates and an increase in respiratory metabolism