Microarray profiling of rats treated for 21 days with Lithium chloride (0.2% in chow), Lamotrigine (30 mg/kg), or appropriately matched vehicles
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
PROVIDER: GSE66276 | GEO | 2015/03/16
SECONDARY ACCESSION(S): PRJNA276308
REPOSITORIES: GEO
Similar Datasets
Project description:Lithium is a first-line treatment for bipolar disorder, where it acts as a mood-stabilizing agent. Although its precise mechanism remains unclear, neuroimaging studies have shown that lithium accumulates in the hippocampus and that chronic use amongst bipolar disorder patients is associated with larger hippocampal volumes. Here, we tested the chronic effects of low (0.75 mM) and high (2.25 mM) doses of lithium on human hippocampal progenitor cells and used immunocytochemistry to investigate the effects of lithium on cell parameters implicated in neurogenesis. Corresponding RNA-sequencing and gene-set enrichment analyses were used to evaluate whether genes affected by lithium in our model overlap with those regulating the volume of specific layers of the dentate gyrus. We observed that high-dose lithium treatment in human hippocampal progenitors increased the generation of neuroblasts (P ≤ 0.01), neurons (P ≤ 0.01), and glia (P ≤ 0.001), alongside the expression of genes which regulate the volume of the molecular layer of the dentate gyrus. This study provides empirical support that adult hippocampal neurogenesis and gliogenesis are mechanisms that could contribute to the effects of lithium on human hippocampal volume.
2021-09-30 | GSE184930 | GEO
Project description:Sodium valproate (VPA) and lithium are mood stabilizers, widely prescribed in the treatment of bipolar disorder, and yet the precise modes of therapeutic action for these drugs are not fully understood. After exposure of the rat serotonergic cell line RN46A to VPA, RNA-sequencing (RNA-Seq) analysis showed widespread changes in gene expression but no changes with lithium. Analysis by multiple pipelines revealed that as many as 230 genes were significantly upregulated and 72 genes were significantly downregulated in response to VPA exposure.
2020-03-07 | GSE146493 | GEO
Project description:Small molecules, BIO and Lithium chloride are widely used to activate Wnt signaling. It has been shown that these molecules induced beta-catenin accumulation and translocation, leading to the activation of Wnt signaling. These molecules also control various cell responses. Here, the differential gene expression of human dental pulp stem cells treated with BIO and Lithium chloride was examined using a high throughput RNA sequencing technique. Results demonstrated that BIO and Lithium chloride regulated the mRNA expression of various genes in human dental pulp stem cells.
2022-08-17 | GSE183633 | GEO
Project description:SD rats were dosed with gold standard antipsychotic therapies, haloperidol or risperidone, at doses aimed at achieving therapeutically relevant drug exposures. Tissues were collected after 21 days of delivery to examine the impact of this treatment on gene expression in frontal cortex, hippocampus and striatum.
2015-03-16 | GSE66275 | GEO
Project description:Wild type strain CEN.PK113-7D was grown in an aerobic batch cultivation with a start concentration of 20 g/L galactose. During exponential growth at a biomass concentration of 3 g dry weight/L LiCl was added to a concentration of 10 mM. Just before addition of LiCl (time 0) and 20, 40, 60 and 140 minutes after addition of LiCl samples were taken for transcription analysis. Lithium inhibits phosphoglucomutase whereby both galactose uptake and growth is strongly affected.
2007-07-07 | E-GEOD-461 | biostudies-arrayexpress
Project description:BACKGROUND: Bipolar disorder (BD) is a highly heritable mood disorder with complex genetic architecture and poorly understood etiology. Previous transcriptomic BD studies have had inconsistent findings due to issues such as small sample sizes and difficulty in adequately accounting for confounders like medication use. METHODS: We performed a differential expression analysis in a well-characterized BD case-control sample (Nsubjects = 480) by RNA sequencing of whole blood. We further performed co-expression network analysis, functional enrichment, and cell type decomposition, and integrated differentially expressed genes with genetic risk. RESULTS: While we observed widespread differential gene expression patterns between affected and unaffected individuals, these effects were largely linked to lithium treatment at the time of blood draw (FDR < 0.05, Ngenes = 976) rather than BD diagnosis itself (FDR < 0.05, Ngenes = 6). These lithium-associated genes were enriched for cell signaling and immune response functional annotations, among others, and were associated with neutrophil cell-type proportions, which were elevated in lithium users. Neither genes with altered expression in cases nor in lithium users were enriched for BD, schizophrenia, and depression genetic risk based on information from genome-wide association studies, nor was gene expression associated with polygenic risk scores for BD. CONCLUSIONS: These findings suggest that BD is associated with minimal changes in whole blood gene expression independent of medication use but emphasize the importance of accounting for medication use and cell type heterogeneity in psychiatric transcriptomic studies. The results of this study add to mounting evidence of lithium's cell signaling and immune-related mechanisms.
2019-10-24 | GSE124326 | GEO
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver from Sprague Dawley rats dosed with myclobutanil (300 mg/kg/day), propiconazole (300 mg/kg/day), or triadimefon (175 mg/kg/day) for 72 hours. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism and fatty acid metabolism were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 12 liver samples were analyzed. Three biological replicates each for the controls, 300 mg/kg/day myclobutanil, 300 mg/kg/day propiconazole, and 175 mg/kg/day triadimefon.
2008-04-08 | E-GEOD-10409 | biostudies-arrayexpress
Project description:Purpose: The goal of this study is to understand the role of co-administred amiloride. This was derived through RNAseq of kidney cortex and determining differential genes in response to lithium, lithium+amiloride and control at 14 days, 28 days and 6 months. Methods: RNAseq of kidney cortex treated with either lithium alone, lithium+amiloride or control. Deseq2 was performed using contrast argument with Wald test to identify significant differentially expression genes at each time point individually. Result & Conclusion: Co-administration with amiloride at all time points contributed in the reduction of inflammation and fibrosis caused by lithium.
2022-08-31 | GSE178950 | GEO
Project description:The purpose of the experiment was to better understand the effects of antimigratory drugs lithium chloride and 6-bromoindirubin-3'-oxime (BIO) in glioblastoma cells. U251 cells were grown to 60-70% confluency in DMEM containing 10% FBS in 6 well plates. Drugs were added (LiCl 20 mM, BIO 5 micromolar, with carrier controls; either NaCl or DMSO) and incubated for 24 hours. Cells were then harvested and RNA purified using TRIZOL.
2023-03-20 | E-MTAB-12775 | biostudies-arrayexpress
Project description:Lithium has been used for more than 50 years as the primary therapy for bipolar affective disorder (BPD) and is highly effective in its treatment. However, the molecular and cellular mechanisms underlying the lithium’s therapeutic action still remains elusive. The goal of the proposed study is to identify genes involved in the lithium-responsive neurological pathway using the fruit fly as a model organism. Based on the fact that the fundamental molecular and cellular mechanisms are well conserved between the fruit fly and vertebrates, the outcomes of this project are expected to lead to the recognition of uncharacterized players or processes responsible for the lithium action in the vertebrates, which would open up the future possibility to develop novel and improved therapies for BPD. The proposed gene-profiling experiment is designed to identify candidate genes and genetic pathways involved in the lithium-responsive biological process. Specific aims of this project are; 1) identify genes whose expression levels are significantly different between the wild type and Shu, 2) identify genes whose expression levels are enhanced or suppressed after lithium treatment, and 3) identify genes whose expression is differentially regulated in the wild type and Shu after lithium treatment. We expect that the genes identified through the proposed microarray analysis will provide important clues for elucidating the molecular and cellular processes responsible for the lithium action. A Drosophila mutant Shudderer (Shu) exhibits various neurological phenotypes, including hyperactivity, uncoordinated movements, and sporadically occurring jerks. Interestingly, many of these phenotypes are greatly suppressed by lithium with the internal concentrations used for treatment of human BPD patients. In addition, Shu mutant is more resistant to the toxic effects of lithium than the wild type strain. These data have led us to the hypothesis that the biological process responsive to lithium is affected in the Shu mutant. We expect that we will be able to identify genes and genetic pathways involved in the lithium-responsive process by comparing the gene expression profiles between the wild type and the Shu mutant with or without lithium treatment. Newly eclosed Canton-S (wild type) and Shu mutant females will be placed in vials containing fly food with or without 50mM LiCl. They will be cultured at 25oC with 65% humidity for 5 days. Three groups of fifty flies (150 flies in total) will be collected for each experimental condition (i.e., genotype and lithium treatment) and frozen on dry ice. The head will be separated and total RNA will be extracted from each group using the TRIzol Reagent (Life Technologies) followed by an RNeasy (Qiagen) cleanup step and a DNase I digestion step. The RNA will be resuspended in DEPC-treated water and the absorbance will be checked at 260 and 280 nm for determination of sample purity and concentration. The GeneChip Drosophila Genome 2.0 Arrays will be used to quantify the levels of transcripts in each sample. The total number of samples will be 4 (2 genotypes and 2 treatments) X 3 (triplicate) = 12. Keywords: dose response
2007-06-30 | GSE8330 | GEO