Gene expression of Lymphoblastoid Cell Lines (LCLs) from Depressed Patients after in-vitro treatment with fluoxetine
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Julia Stingl
PROVIDER: E-GEOD-83386 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:We used whole gene gene expression profiling to identify potential gene expression biomarkers associated for the treatment individualization of depressive disorders.
2016-06-15 | GSE83386 | GEO
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Project description:Both the mechanism of action and the factors determining the behavioral response to antidepressants are unknown. It has been shown that antidepressant treatment promotes the proliferation and survival of hippocampal neurons via enhanced serotonergic signaling, but it is still unclear whether hippocampal neurogenesis is responsible for the behavioral response to antidepressants. Furthermore, a large subpopulation of patients fails to respond to antidepressant treatment due to presumed underlying genetic factors. In the present study, we have used the phenotypic and genotypic variability of inbred mouse strains to show that there is a genetic component to both the behavioral and neurogenic effects of chronic fluoxetine treatment, and that this antidepressant induces an increase in hippocampal cell proliferation only in the strains that also show a positive behavioral response to treatment. The behavioral and neurogenic responses are associated with an upregulation of genes known to promote neuronal proliferation and survival. These results suggest that inherent genetic predisposition to increased serotonin-induced neurogenesis is a determinant of antidepressant efficacy. Experiment Overall Design: Male DBA/2J, age 3-5 weeks, were obtained from The Jackson Laboratory (Bar Harbor, ME) and maintained on a 12:12 light:dark cycle with lights on at 0700 hours. Following at least one week of acclimation, mice were provided with either untreated or fluoxetine-treated drinking water, available ad libitum. Fluoxetine-HCl was obtained from Spectrum Chemicals (Gardena, CA). Differences in daily water consumption were previously determined by measuring water intake for three weeks from at least 12 mice (6.4 mL (+/- .58 mL) per day). We also determined the average weight at 10 weeks of age (25.5 g +/- 1.4 g), and used this information to dilute fluoxetine in the water in order to provide a daily dosage of 0 or 18 mg/kg/mouse. Experiment Overall Design: Mice were 8-12 weeks of age at the time of behavioral testing, which was performed during the light phase between 1300h and 1600h. Behavioral despair was measured using a mouse Tail Suspension apparatus from Med Associates (Georgia, VT). Experiment Overall Design: Individual bilateral hippocampii from 21-day-treatment 0 and 18 mg/kg/day DBA/2J mice were homogenized in 500 µl TRIzol using a QIAgen Tissuelyser (15 minutes at 30 Hz, QIAgen, Chatsworth, CA). RNA was extracted by phenol-chloroform phase separation and further processed using the RNAeasy miniprep kit (QIAgen). For each treatment group of 12 animals, separate RNA pools were made using hippocampal RNA from 6 mice per pool. These biological replicates were processed separately through the entirety of the microarray procedure. Five µg of total RNA from each pool was used as a template to synthesize complementary DNA (cDNA) and biotinylated cRNA (Enzo kit, Affymetrix, Santa Clara, CA) using standard Affymetrix protocols. cRNA was hybridized to Affymetrix GeneChip Mouse Genome 430 2.0 Array. Data were analyzed using ArrayAssist software (Stratagene, La Jolla, CA) and normalized with the GCRMA algorithm. A probeset had to obtain a minimal intensity value 100 to be considered as detecting expression above background. Therefore, any probeset that failed to meet this cutoff was removed from the analysis. Ratios of intensity differences were generated and genes showing at least a two-fold difference between experimental conditions were identified for further analysis.
2008-06-14 | E-GEOD-6476 | biostudies-arrayexpress
Project description:Investigation of 5-aza-2'-cytidine and trichostatin A effect to gene expression of human LCLs. LCLs estabulished from patients with genetic dissease are commonly used for mRNA or protein analysis of disease related genes. However, ofen times the gene of interset is not expressed in LCL. Epigenetic modification could be overcome this problem. Expression array study with total RNA extracted from normal male derived LCLs with eight 60-mer probe per gene. 47633 exemplar genes representing a total of 63780 transcripts variants.
2012-01-27 | E-GEOD-35359 | 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:MicroRNAs are a wide class of ~22 nt non-coding RNAs of metazoans capable of inhibiting target mRNAs translation by binding to partially complementary sites in their 3âUTRs. Due to their regulatory potential, miRNAs are implicated in functioning of a broad range of biological pathways and processes. Here we investigate the functions of the miR-959-964 cluster expressed predominantly in testes of Drosophila melanogaster. The deletion of miR-959-964 resulted in male sterility due to the disturbance of the spermatid individualization process. Analysis of the transcriptome by microarray followed by luciferase reporter assay revealed didum, for, fdl and CG10512 as the targets of miR-959-964. Moreover, the deletion of miR-959-964 is accompanied by a decreased the expression of genes responsible for microtubule-based movement and spermatid differentiation. Thus, we suggest that miR-959-964 can control the process of spermatid individualization by direct and indirect modulating the expression of different components of the individualization process. In addition, we have shown that in comparison to other miRNAs, the rate of evolution of the testis-specific miR-959-964 cluster is unusually high, indicating its possible involvement in speciation via reproductive isolation.
2015-10-29 | E-MTAB-3214 | biostudies-arrayexpress
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:to understand the consequences of chronic exposure to fluoxetine during postnatal life on global transcriptional changes withing the rat hippocamps Agilent one-color experiment,Organism: Rattus Norvegicus, Agilent-016352 Genotypic designed Custom Rattus Norvegicus 8x15k, Labeling kit: Agilent Quick-Amp labeling Kit (p/n5190-0442)
2013-12-01 | E-GEOD-42940 | biostudies-arrayexpress
Project description:Investigation of human X-linked imprinted gene. Comparing pooled RNA of lymphoblastoid cell lines from normal human male and female, identify the genes expressed with sex spesific manner. Expression array study with total RNA extracted from pooled male and female LCLs with eight 60-mer probe per gene. 47633 exemplar genes representing a total of 63780 transcripts/variants.
2012-01-20 | E-GEOD-35207 | biostudies-arrayexpress