Transcriptome profiles of mouse cortical cultures and the brain treated with fluoxetine, sertraline or citalopram
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ABSTRACT:
PROVIDER: PRJNA1242215 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR32864500_1.fastq.gz | Fastqsanger.gz | |||
| SRR32864500_2.fastq.gz | Fastqsanger.gz | |||
| SRR32864501_1.fastq.gz | Fastqsanger.gz | |||
| SRR32864501_2.fastq.gz | Fastqsanger.gz | |||
| SRR32864502_1.fastq.gz | Fastqsanger.gz |
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Project description:Selective serotonin reuptake inhibitors (SSRIs) are one of the most prescribed antidepressant classes in recent decades, with the development of numerous variants. While the primary action of these medications involves the inhibition of serotonin reuptake, the observed therapeutic efficacy exhibits interindividual variability. In order to elucidate the molecular mechanisms underlying their pharmacological actions, this study examined the alteration in the transcriptome following treatment of each SSRI—fluoxetine, sertraline, or citalopram— or vehicle in cultured cortical neurons and the medial prefrontal cortex (mPFC) of mice (Mus musculus, Slc:ICR).
2025-03-30 | GSE292948 | 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).
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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.
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Project description:This SuperSeries is composed of the following subset Series: GSE35751: Comparative analysis of S100a10-expressing cortical pyramidal cells and whole cortex GSE35758: Comparative analysis of S100a10 and Glt25d2 cortical pyramidal cells GSE35761: Effect of fluoxetine treatment on translational profiles of S100a10 cortical pyramidal cells GSE35763: Effect of fluoxetine treatment on translational profiles of Glt25d2 cortical pyramidal cells GSE35765: Effect of fluoxetine treatment on translational profiles of S100a10 cortical pyramidal cells in p11 KOs Refer to individual Series
2012-05-31 | E-GEOD-35766 | biostudies-arrayexpress
Project description:Molecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from S100a10-expressing corticostriatal projection neurons. We show that the S100a10 cells are a unique population of cortical cells that are strongly and specifically responsive to chronic SSRI administration and that this response requires p11 (the protein product of S100a10). Our data demonstrate that the beneficial actions of antidepressant therapy can be mediated by a single cell type that is positioned to normalize activity between cortical and subcortical sites, and suggest that development of drugs that specifically target the activity of these cells may result in improved therapies to treat depression. S100a10 bacTRAP mice were administered either fluoxetine (FLX) or vehicle (VEH) in their drinking water for 15-18 days. Three independent TRAP replicates from the cortex of each group were then collected. Total RNA from the immunoprecipitates was amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the S100a10 BAC labels some non-neuronal cells, we recommend only probe sets listed in Table S1 of the accompanying paper be included in the analysis.
2012-05-31 | E-GEOD-35761 | biostudies-arrayexpress
Project description:Molecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from S100a10-expressing corticostriatal projection neurons. We show that the S100a10 cells are a unique population of cortical cells that are strongly and specifically responsive to chronic SSRI administration and that this response requires p11 (the protein product of S100a10). Our data demonstrate that the beneficial actions of antidepressant therapy can be mediated by a single cell type that is positioned to normalize activity between cortical and subcortical sites, and suggest that development of drugs that specifically target the activity of these cells may result in improved therapies to treat depression. Glt25d2 bacTRAP mice were administered either fluoxetine (FLX) or vehicle (VEH) in their drinking water for 15-18 days. Three independent TRAP replicates from cortex of each group were then collected. Total RNA from the immunoprecipitates was amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the S100a10 BAC labels some non-neuronal cells, we recommend only probe sets listed in Table S1 of the accompanying paper be included in the analysis.
2012-05-31 | E-GEOD-35763 | biostudies-arrayexpress
Project description:Molecular phenotyping of cell types and neural circuits underlying pathological neuropsychiatric conditions and their responses to therapy provides one avenue for the development of more specific and effective treatments. In this study, we identify a cell population in the cerebral cortex that shows robust and specific molecular adaptations following long-term SSRI treatment. We employed the bacTRAP strategy, which uses BAC transgenic mice expressing EGFP-tagged ribosomal protein L10a in specific cell populations, to affinity purify polysome-bound mRNAs from S100a10-expressing corticostriatal projection neurons. We show that the S100a10 cells are a unique population of cortical cells that are strongly and specifically responsive to chronic SSRI administration and that this response requires p11 (the protein product of S100a10). Our data demonstrate that the beneficial actions of antidepressant therapy can be mediated by a single cell type that is positioned to normalize activity between cortical and subcortical sites, and suggest that development of drugs that specifically target the activity of these cells may result in improved therapies to treat depression. S100a10 bacTRAP mice crossed to constitutive p11 KO mice (S100a10 bacTRAP/p11 KO) were administered either fluoxetine (FLX) or vehicle (VEH) in their drinking water for 15-18 days. Three independent TRAP replicates from the cortex of each group were then collected. Total RNA from the immunoprecipitates was amplified and hybridized. Data were normalized with the GCRMA algorithm and replicates were averaged across conditions. We recommend filtering data to remove probe sets with normalized expression values less than 50 in at least one condition. Because the S100a10 BAC labels some non-neuronal cells, we recommend only probe sets listed in Table S1 of the accompanying paper be included in the analysis.
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