Antidepressants are widely used for treatment of depression. Imipramine, a typical antidepressant, is recently known to have an effect to restore the expression of brain-derived neurotrophic factor gene, which is decreased in depressed patients, by increasing histone acetylation. However, it is largely unknown whether other antidepressants have similar epigenetic effects to change gene expression. To address this question, we examined the effect of five antidepressants (imipramine, citalopram, duloxetine, amitriptyline, mirtazapine) on expression of genes associated with mental and neurodegenetative disorders. We found that 48-hour treatment with imipramine, citalopram, amitriptyline, mirtazapine, but not duloxetine, caused a large number of differentially expressed genes in primary neocortical neurons in mice. Focused on genes relating to neural protection and neuroplasticity, we discovered that amitriptyline not only enhanced the expression of atf3 and cox2 by increasing histone H3 Lys4 trimethylation (H3K4me3), but also protected neurons against oxygen-glucose deprivation and staurosporine-induced apoptosis. Our study will shed a new insight in understanding of the molecular and epigenetic mechanism of antidepressants.
No associated publication
Specimen part
View SamplesTransforming growth factor (TGF)- plays crucial roles in embryonic development and adult tissue homeostasis by eliciting various cellular responses in target cells. TGF- signaling is principally mediated through receptor-activated Smad proteins, which regulate expression of target genes in cooperation with other DNA-binding transcriptionfactors (Smad cofactors). In this study, we found that the basic helix-loop-helix transcription factor Olig1 is a Smad cofactor involved in TGF-b-induced cell motility. Knockdown of Olig1 attenuated TGF--induced cell motility in chamber migration and wound healing assays. In contrast, Olig1 knockdown had no effect on bone morphogenetic protein-induced cell motility, TGF--induced cytostasis or epithelial-mesenchymal transition. Furthermore, we observed that cooperation of Smad2/3 with Olig1 is regulated by a peptidyl-prolyl cis/trans isomerase, Pin1. TGF-b-induced cell motility, induction of Olig1-regulated genes, and physical interaction between Smad2/3 and Olig1 were all inhibited after knockdown of Pin1, indicating a novel mode of regulation of Smad signaling. We also found that Olig1 interacts with the L3 loop of Smad3. Using a synthetic peptide corresponding to the L3 loop of Smad3, we succeeded in selectively inhibiting TGF-b-induced cell motility. These findings may lead to a new strategy for selective regulation of TGF-b-induced cellular responses.
Oligodendrocyte transcription factor 1 (Olig1) is a Smad cofactor involved in cell motility induced by transforming growth factor-β.
Specimen part
View SamplesTime dependent-profiles in the gene expression level following lateral moderate fluid percussion injury in the rat brain
Genetic and histologic evidence implicates role of inflammation in traumatic brain injury-induced apoptosis in the rat cerebral cortex following moderate fluid percussion injury.
Sex, Age, Specimen part, Time
View SamplesThe purpose of this study was to characterize the transcriptional effects induced by subcutaneous IFN-beta-1b treatment (Betaferon, 250 g every other day) in patients with relapsing-remitting form of multiple sclerosis (MS).
Long-term genome-wide blood RNA expression profiles yield novel molecular response candidates for IFN-beta-1b treatment in relapsing remitting MS.
Sex
View SamplesThis SuperSeries is composed of the SubSeries listed below.
No associated publication
Specimen part
View SamplesGene expression profile comparison from fibroblasts of Huntington individuals and normal ones
Gene expression profile in fibroblasts of Huntington's disease patients and controls.
Sex, Age, Specimen part, Disease
View SamplesComparison of the differential expression mRNA profiles from the brain cortex of hypoxia and normaixa rats by silica microarray chip
No associated publication
Specimen part
View SamplesBone mineral density and structure candidate gene analysis in alcohol-non-preferring (NP), alcohol-preferring (P), congenic NP (NP.P) and congenic P (P.NP) rats
Identification of genes influencing skeletal phenotypes in congenic P/NP rats.
No sample metadata fields
View SamplesFemoral neck bone mineral density and structure candidate gene analysis in Fischer 344 (F344) and Lewis (LEW) rats
Genomic expression analysis of rat chromosome 4 for skeletal traits at femoral neck.
No sample metadata fields
View SamplesGene expression was measured using microarrays in 8 hour postfertilization embryos, comparing control versus ethanol-treated (2 to 8 hours postfertilization) embryos. This experiment was performed to determine the gene expression changes that occur in response to ethanol treatment as a model of fetal alcohol spectrum disorder.
Ethanol exposure disrupts extraembryonic microtubule cytoskeleton and embryonic blastomere cell adhesion, producing epiboly and gastrulation defects.
Age, Specimen part, Treatment
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