Microarray analysis of the leukocyte global gene expression profile following lithium treatment
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44987 | GEO | 2013/03/09
SECONDARY ACCESSION(S): PRJNA192713
REPOSITORIES: GEO
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Project description:To further development of our gene expression approach to lithium pharmacodynamics, we have employed whole genome microarray expression profiling as a discovery platform to identify genes with the potential to distinguish lithium pharmacodynamics across an exposure range relevant for medical decision-making in lithium therapy. 8 healthy male subjects participated in this study. Lithium was prescribed for 2 weeks, enough to reach a therapeutic serum concentration (0.6-1.0mM). Leukocyte counts and serum lithium concentrations were determined at baseline (before medication), after 1 week and 2 weeks medication and post-2-weeks (2 weeks after stopping medication). Gene expression profiling was performed at each time point using Agilent G4112F Whole Human Genome arrays containing approximately 44,000 probe sets. Some of the candidate gene expressions were also determined by real-time PCR. Lithium-induced gene expression in human blood was measured at baseline, after 1 week and 2 weeks of treatment, and after 2 weeks after stopping medication. 4 independent experiments were performed (baseline, 1wk, 2wk, after 2wk) using mixed samples from each donor.
2013-03-09 | E-GEOD-44987 | 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:We determined lithium cobalt oxide LCO’s effects on pathways in the model organism Daphnia magna through RNA-Seq global gene expression analysis.
2022-05-03 | GSE174016 | GEO
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:Rationale: Familial adenomatous polyposis (FAP) syndrome is characterized by the development of numerous colorectal polyps. If left untreated, these patients have a chance of nearly 100% of developing colorectal cancer (CRC) at a young age. Therefore, guidelines recommend a prophylactic colectomy during early adulthood. Even after colectomy, most patients will develop adenomas in the retained rectum or ileoanal pouch requiring further endoscopic surveillance. In a recent study in mouse models, a chemopreventive effect of Lithium was observed on the spread of Apc mutated cells within the crypts of normal intestinal mucosa, suggesting polyp formation can be prevented. Lithium is used to treat patients with bipolar disorders but has never been investigated in patients with FAP aiming to reduce polyp burden. We hypothesize that Lithium could reduce the spread of APC mutated cells within the crypt of normal intestinal mucosa potentially reducing polyp burden in patients with FAP.
Objective: The aim of this study is to investigate the effect of low-dose Lithium on stem cell dynamics, the number and size of polyps and, to assess safety outcomes of this drug in FAP patients.
Study design: A prospective phase II, single arm pilot trial, with a duration of 18 months. The drug will be administered between month 6 and 12.
Study population: Twelve patients with FAP between the age of 18 and 35 not having undergone a colectomy (yet), having a genetically confirmed APC mutation and a family history with a classical FAP phenotype.
Intervention: All patients will be treated with Lithium with an oral dose of 300mg a day for six months, achieving a therapeutic serum level between 0.2-0.4 mmol/L.
Main study parameters/endpoints: The main outcome parameter is the effect of Lithium on the spread of APC mutant cells within intestinal crypts over time by using an APC specific marker NOTUM (a significance reduce of fixed crypts and reduction of fixed clone size of 50%).
Nature and extent of the burden and risks associated with participation, benefit and group relatedness: A physical examination and an endoscopy with biopsies will be performed at baseline and every six months (four in total). Laboratory testing will be done at baseline and every two months during Lithium treatment. Patients will be interviewed by phone and Lithium side effect questionnaires will be obtained at baseline and during Lithium treatment. Lithium serum levels will be measured at day 12 and 22 after start of the study drug (at month 6). When the therapeutic range has been achieved, serum level testing will be done every month. Most relevant side-effects that could potential occur include polyuria, hyperparathyroidism and hypothyroidism. Most side effects are dose-dependent and will be regularly monitored. Patients with FAP could potentially benefit from a chemopreventive therapy such as Lithium to postpone or even avoid invasive types of surgery.
| 2733032 | ecrin-mdr-crc
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:Bipolar disorder is a severe and heritable psychiatric disorder and affects up to 1% of the population worldwide. Lithium is recommended as first-line treatment for the maintenance treatment of bipolar-affective disorder in current guidelines, its molecular modes of action are however poorly understood. Cell models derived from bipolar patients could prove useful to gain more insight in the molecular mechanisms of bipolar disorder and the common pharmacological treatments. As primary neuronal cell lines cannot be easily derived from patients, peripheral cell models should be evaluated in their usefulness to study pathomechanisms and the mode of action of medication as well as in regard to develop biomarkers for diagnosis and treatment response.
2018-12-01 | GSE66196 | GEO
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
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
Project description:Our previous work in a Drosophila model of Alzheimer's disease (AD) has shown that we can intervene into the pathways to slow or prevent AD progression. Lithium was able to rescue toxicity in the Drosophila AD model which corresponded with a reduction in Abeta levels. Furthermore, we have demonstrated that Lithium affects Abeta protein translation. To this end, we were interested in studying the effect of Lithium on Abeta using microarray analyses, to determine if we could uncover any interesting downstream pathways. Flies were expressing a mutant version of Abeta, the Arctic mutation, which increases the aggregation or production of Abeta (UAS-ArcAb42/+;elavGS/+). We collected flies 2 days post eclosion that either had no Arctic Abeta protein, or expressed Arctic with or without Lithium treatment for 17 days post eclosion. Samples were homogenised using RLT buffer with betamercaptoethanol.
2017-01-26 | E-MTAB-4611 | biostudies-arrayexpress