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Microarray profiling of rats treated for 21 days with Lithium chloride (0.2% in chow), Lamotrigine (30 mg/kg), or appropriately matched vehicles

ABSTRACT: SD rats were dosed with gold mood stabilizer therapies, lithium or lamotrigine, 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.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE66276 | GEO | 2015/03/16

SECONDARY ACCESSION(S): PRJNA276308

REPOSITORIES: GEO

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Lithium treatment and human hippocampal neurogenesis

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

Transcriptional analysis of sodium valproate and lithium in a serotonergic cell line

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.

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Microarray profiling of rats treated for 21 days with haloperidol (0.25 mg/kg/d), risperidone (5 mg/kg/d) or vehicle

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

Differential gene expression of Wnt agonist (BIO and lithium chloride) treated human dental pulp stem cells

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

Transcription profiling of galactose-grown S. cerevisiae cells exposed to lithium chloride

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

Whole blood transcriptome analysis in bipolar disorder reveals strong lithium effect

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

Transcription profiling of total of rat liver samples treated with 300 mg/kg/day myclobutanil, 300 mg/kg/day propiconazole, and 175 mg/kg/day triadimefon

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

Effects of amiloride in lithium induced kidney interstitial fibrosis

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

Signaling Mechanisms in Initiation of Lithium-Induced Nephrogenic Diabetes Insipidus

Project description:Lithium treatment is commonly used to treat bipolar disorder. However, this treatment disrupts kidney fuctionality. We used microdissected cortical collecting ducts to study proteomics and ultimately discover what changes occur in protein expression after 72-hr lithium treatment.

2019-07-01 | PXD010118 | Pride

The effects of antimigratory drugs lithium chloride and 6-bromoindirubin-3'-oxime (BIO) in glioblastoma cells

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

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