Identification of metabolic pathways in Daphnia magna exposed to selective serotonin reuptake inhibitors using transcriptomic, immunocytochemistry and physiological responses.
Ontology highlight
ABSTRACT:
ORGANISM(S): Daphnia magna
PROVIDER: GSE45053 | GEO | 2013/03/15
SECONDARY ACCESSION(S): PRJNA193086
REPOSITORIES: GEO
Similar Datasets
Project description:Assessing the risks of long-term exposure to low doses of pharmaceuticals is an identified research need, particularly for those that may act as neural disruptors in non-vertebrate species. Selective serotonin reuptake inhibitors (SSRIs) act by blocking the re-uptake of serotonin in the nerve synapses, increasing the effective concentration of serotonin in the intra-synaptic space and therefore stimulating serotoninergic neurons. This effect is used worldwide to treat clinical depression in humans, with the consequence of their widespread release into the environment. SSRIs have been found to alter the reproductive physiology of D. magna and other invertebrates in a biphasic way. Low levels of fluoxetine stimulated offspring production in Daphnia magna and Ceriodaphnia dubia at 36 and 50 µg/l, respectively, but higher exposure levels inhibited reproduction in the same species. In this study we explore the hypothesis that SSRI can affect D. magna juvenile developmental rates and offspring production disrupting serotonin activity that is known to regulate carbohydrate and oxidative metabolic pathways. The primary mode of action was tested using transcriptomic analyses of juveniles and adults exposed to SSRIs (fluoxetine 80 ppbs, fluovoxamine 30 ppbs) and serotonin-immunocytochemistry assays of D. magna brains. Reproduction, respirometry and biochemical measurements allowed to related gene and immunological base effects to phenotypic responses.
2013-03-15 | E-GEOD-45053 | biostudies-arrayexpress
Project description:Selective serotonin reuptake inhibitors (SSRIs) are commonly prescribed antidepressant drugs in pregnant women. Given that SSRIs can cross the placental and blood-brain barriers, these drugs potentially affect serotonergic neurotransmission and neurodevelopment in the fetus. Although no gross SSRI-related teratogenic effect has been reported, infants born following prenatal exposure to SSRIs have a higher risk for various behavioral abnormalities. Therefore, we examined the effects of prenatal fluoxetine, the most commonly prescribed SSRI, on social and cognitive behavior in mice. Intriguingly, chronic in utero fluoxetine treatment impaired working memory and social novelty recognition in adult males with augmented spontaneous inhibitory synaptic transmission onto the layer 5 pyramidal neurons in the medial prefrontal cortex (mPFC). Moreover, fast-spiking interneurons in the layer 5 mPFC exhibited enhanced basal intrinsic excitability, augmented serotonin-induced neuronal excitability, and increased inhibitory synaptic transmission onto the layer 5 pyramidal neurons due to augmented 5-HT2A receptor (5-HT2AR) signaling. More importantly, the observed behavioral deficits of in utero fluoxetine-treated mice could be reversed by acute systemic application of 5-HT2AR antagonist. Taken together, our findings support the notion that alterations in serotonin-mediated inhibitory neuronal modulation result in reduced cortical network activities and cognitive impairment following prenatal exposure to SSRIs.
2018-03-07 | GSE111491 | GEO
Project description:Lactation causes dramatic maternal calcemic adaptations where up to 10% of maternal bone density is mobilized for milk calcium. Serotonin plays a role in regulating this calcemic demand through alterations in DNA methylation. Selective serotonin reuptake inhibitors used to treat peripartum depression exacerbate this signaling. The first objective of this study was to determine the impact of fluoxetine, one of the most popular selective serotonin reuptake inhibitors, on the transcriptome of the mouse mammary gland during peak lactation. The second objective was to determine whether supplementation with folic acid, a well-known methyl donor, would mitigate the gene expression changes induced by fluoxetine.
2021-11-22 | GSE188845 | GEO
Project description:Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 µg/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip® Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek® Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 µg/L and 131 at 250 µg/L; and after sertraline exposure was 33 at 25 µg/L and 52 at 250 µg/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish.
2012-09-06 | GSE31712 | GEO
Project description:Pharmaceutical chemicals used in human medicine are released into surface waters via municipal effluents and pose a risk for aquatic organisms. Among these substances are selective serotonin reuptake inhibitors (SSRIs) which can affect aquatic organisms at sub ppb concentrations. To better understand biochemical pathways influenced by SSRIs, evaluate changes in the transcriptome, and identify gene transcripts with potential for biomarkers of exposure to SSRIs; larval zebrafish Danio rerio were exposed (96 h) to two concentrations (25 and 250 µg/L) of the SSRIs, fluoxetine and sertraline, and changes in global gene expression were evaluated (Affymetrix GeneChip® Zebrafish Array). Significant changes in gene expression (>=1.7 fold change, p<0.05) were determined with Partek® Genomics Suite Gene Expression Data Analysis System and ontology analysis was conducted using Molecular Annotation System 3. The number of genes differentially expressed after fluoxetine exposure was 288 at 25 µg/L and 131 at 250 µg/L; and after sertraline exposure was 33 at 25 µg/L and 52 at 250 µg/L. Five genes were differentially regulated in all treatments relative to control, suggesting that both SSRIs share some similar molecular pathways. Among them, expression of the gene coding for FK506 binding protein 5 (FKBP5), which is annotated to stress response regulation, was highly down-regulated in all treatments (results confirmed by qRT-PCR). Gene ontology analysis indicated that regulation of stress response and cholinesterase activity were critical functions influenced by these SSRIs, and suggested that changes in the transcription of FKBP5 or acetylcholinesterase could be useful biomarkers of SSRIs exposure in wild fish. Zebrafish (Danio rerio) were obtained from the Zebrafish Research Facility maintained at the Center for Environmental Biotechnology at the University of Tennessee. Fish husbandry, spawning, and experimental procedures were conducted with approval from the UT Insititutional Animal Care and Use Committee (Protocol #1690-1007). Water for holding fish and conducting experiments (hereafter referred to as fish water) consisted of MilliQ water (Millipore, Bedford, MA) with ions added: 19 mg/L NaHCO3, 1 mg/L sea salt (Instant Ocean Synthetic Sea Salt, Mentor, OH), 10 mg/L CaSO4, 10 mg/L MgSO4, 2 mg/L KCl. Embroyos were obtained by spawning adult fish with no history of contaminant exposure. Fertilization of embryos took place at the same time (<15 minutes), such that larvae used in experiments were of similar age at the time of exposure. All activities (maintenance of adult fish, spawning, and experiments) were conducted in an environmental chamber with a temperature of 27 +/- 1 C and 14:10h light:dark photoperiod. Larval zebrafish (72 hpf) were exposed for 96 h in 200ml fish water containing appropirate amount of SSRI stock (i.e. fluoxetine or sertraline). There were four SSRIs treatments (25 and 250 ug/L fluoxetine and 25 and 250 ug/L sertraline) and one control (no SSRIs) with triplicate beakers and each beaker contained about 100 larval fish. During exposure for 96 hours, beakers were kept covered to prevent water evaporation and fish were not fed (i.e., fish consumed their yolk sac).
2012-09-06 | E-GEOD-31712 | biostudies-arrayexpress
Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals. 38 samples, 2 dentate regions (dorsal/ventral), 3 groups (control, antidepressant resistant (4 mice), antidepressant responsive (7 mice), untreated (8 mice).
2013-12-31 | E-GEOD-43261 | biostudies-arrayexpress
Project description:Identification of metabolic pathways in Daphnia magna exposed to selective serotonin reuptake inhibitors using transcriptomic, immunocytochemistry and physiological responses.
| PRJNA193086 | ENA
Project description:Selective serotonin reuptake inhibitors (SSRIs) such as fluoxetine are the most common treatment for major depression. However, approximately 50% of depressed patients fail to achieve an effective treatment response. Understanding how gene expression systems relate to treatment responses may be critical for understanding antidepressant resistance. Transcriptome profiling allows for the simultaneous measurement of expression levels for thousands of genes and the opportunity to utilize this information to determine mechanisms underlying antidepressant treatment responses. However, the best way to relate this immense amount of information to treatment resistance remains unclear. We take a novel approach to this question by examining dentate gyrus transcriptomes from the perspective of a stereotyped fluoxetine-induced gene expression program. Expression programs usually represent stereotyped changes in expression levels that occur as cells transition phenotypes. Fluoxetine will shift transcriptomes so they lie somewhere between a baseline state and a full-response at the end of the program. The position along this fluoxetine-induced gene expression program (program status) was measured using principal components analysis (PCA). The same expression program was initiated in treatment-responsive and resistant mice but treatment response was associated with further progression along the fluoxetine-induced gene expression program. The study of treatment-related differences in gene expression program status represents a novel way to conceptualize differences in treatment responses at a transcriptome level. Understanding how antidepressant-induced gene expression program progression is modulated represents an important area for future research and could guide efforts to develop novel augmentation strategies for antidepressant treatment resistant individuals.
2013-12-31 | GSE43261 | GEO
Project description:Recent evidence has suggested that fluoxetine, a serotonin-reuptake inhibitor and emerging environmental contaminant, can have non-targeted effects on metabolism in fish exposed to this waterborne pollutant. Using the highest, environmentally relevant, detectable level of fluoxetine (540 ng/L) we examined the impact of fluoxetine on the miRNA profile in the liver of zebrafish that were both fed and fasted for a period of 7 days. These results were further compared to the miRNA profile of zebrafish fasted and fed for 7 days, which were not exposed to fluoxetine. Results indicated that several miRNA that were involved with downregulating genes/pathways in response to fasting were also upregulated in fish exposed to fluoxetine, irrespective to fasting or feeding. These results suggest fluoxetine can have non-targeted effects on metabolic pathways mediated through miRNA expression. Furthermore, specific miRNA (dre-let-7d & dre-miR-140-5p) were found to target the catalytic subunit (AMPKa1 & AMPKa2, respectively) of AMP-Kinase, a master regulator of metabolism. Using predictive software and qPCR validation, combined with the expression profile of these two miRNA, we were able to establish a significant relationship between the expression of these specific miRNA to the downregulation of AMPKa subunit under the influence of 540 ng/L fluoxetine. Adult, female zebrafish were either fed or fasted for 7 days with and without the presense of 540 ng/L fluoxetine, and livers extracted and miRNA purified for miRNA microaary experiment.
2014-02-21 | E-GEOD-55229 | biostudies-arrayexpress
Project description:Daphnia magna is a bio-indicator organism accepted by several international water quality regulatory agencies. Current approaches for assessment of water quality rely on acute and chronic toxicity that provide no insight into the cause of toxicity. Recently, molecular approaches, such as genome wide gene expression responses, are enabling an alternative mechanism based approach to toxicity assessment. While these genomic methods are providing important mechanistic insight into toxicity, statistically robust prediction systems that allow the identification of chemical contaminants from the molecular response to exposure are needed. Here we apply advanced machine learning approaches to develop predictive models of contaminant exposure using a D. magna gene expression dataset for 36 chemical exposures. We demonstrate here that we can discriminate between chemicals belonging to different chemical classes including endocrine disruptors, metals and industrial chemicals based on gene expression. We also show that predictive models based on indices of whole pathway transcriptional activity can achieve comparable results while facilitating biological interpretability. D. magna were exposed to 36 Chemicals and 5 control series in quadruplicate.
2013-01-17 | E-GEOD-43564 | biostudies-arrayexpress