Lithium carbonate alleviates colon inflammation
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PROVIDER: PRJEB46058 | ENA |
REPOSITORIES: ENA
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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: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:RATIONALE: The use of cholecalciferol and calcium carbonate may keep colon cancer from coming back in patients with colon cancer that has been removed by surgery.
PURPOSE: This randomized clinical trial is studying two different doses of cholecalciferol to compare how well they work when given together with calcium carbonate in treating patients with colon cancer that has been removed by surgery.
| 2039759 | ecrin-mdr-crc
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: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.
2013-03-09 | GSE44987 | GEO
Project description:Wnt signaling in essential for osteoblast differentiation and is activated by lithium via inhibition of glycogen synthase kinase 3beta. Although lithium has been shown to enhance osteoblast differentiation in mice models and accelerate bone repair, its effect in humans is not clear. Therefore, we performed gene expression profiling of human MSCs from 3 donors treated with lithium (5mM) for 7 days. Microarray profiling of lithium-stimulated hMSC revealed decreased expression of adipogenic genes (CEBPA, CMKLR1, HSD11B1) and genes involved in lipid biosynthesis. Interestingly, osteoclastogenic factors and immune responsive genes (IL7, IL8, CXCL1, CXCL12, CCL20) were also downregulated. Negative transcriptional regulators of the osteogenic program (TWIST1 and PBX1) were suppressed while genes involved in mineralization like CLEC3B and ATF4 were induced. These results suggest suppression of adipogenic program and induction of osteogenic genes.
2013-02-02 | GSE34747 | 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
Project description:Lithium is the gold standard treatment for bipolar disorder. The goal of this study was to identify gene expression networks associated with lithium response. RNAseq data was obtained from IPSC derived neurons from lithium responders and non-responders. Focal adhesion was the network most associated with response.
2022-06-09 | GSE205422 | GEO