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

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

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

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

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

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

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Additional file 1: of Differential gene transcription across the life cycle in Daphnia magna using a new all genome custom-made microarray

Word file with the qPCR validation of the results in Figure S1 and the total number probes and genes of a given life-stage differential transcribed across the remaining ones and those up and down regulated in Tables S1 and S2 (DOCX 40 kb

Additional file 2: of Differential gene transcription across the life cycle in Daphnia magna using a new all genome custom-made microarray

Excel file with specific genes which were not transcribed (Fluorescence below background) throughout the development stages. (XLSX 89 kb