scholarly journals Transcriptome Changes in Three Brain Regions during Chronic Lithium Administration in the Rat Models of Mania and Depression

2021 ◽  
Vol 22 (3) ◽  
pp. 1148 ◽  
Author(s):  
Dawid Szczepankiewicz ◽  
Piotr Celichowski ◽  
Paweł A. Kołodziejski ◽  
Ewa Pruszyńska-Oszmałek ◽  
Maciej Sassek ◽  
...  
Keyword(s):  
Gene Expression ◽  
Frontal Cortex ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Forced Swim Test ◽  
Lithium Treatment ◽  
Brain Regions ◽  
Non Coding Rnas ◽  
Depressive Episodes

Lithium has been the most important mood stabilizer used for the treatment of bipolar disorder and prophylaxis of manic and depressive episodes. Despite long use in clinical practice, the exact molecular mechanisms of lithium are still not well identified. Previous experimental studies produced inconsistent results due to different duration of lithium treatment and using animals without manic-like or depressive-like symptoms. Therefore, we aimed to analyze the gene expression profile in three brain regions (amygdala, frontal cortex and hippocampus) in the rat model of mania and depression during chronic lithium administration (2 and 4 weeks). Behavioral changes were verified by the forced swim test, open field test and elevated maze test. After the experiment, nucleic acid was extracted from the frontal cortex, hippocampus and amygdala. Gene expression profile was done using SurePrint G3 Rat Gene Expression whole transcriptome microarrays. Data were analyzed using Gene Spring 14.9 software. We found that chronic lithium treatment significantly influenced gene expression profile in both mania and depression models. In manic rats, chronic lithium treatment significantly influenced the expression of the genes enriched in olfactory and taste transduction pathway and long non-coding RNAs in all three brain regions. We report here for the first time that genes regulating olfactory and taste receptor pathways and long non-coding RNAs may be targeted by chronic lithium treatment in the animal model of mania.

scholarly journals Gene Expression Profile in Frontal Cortex in Sporadic Frontotemporal Lobar Degeneration-TDP

2018 ◽  
Vol 77 (7) ◽  
pp. 608-627 ◽  
Author(s):  
Pol Andrés-Benito ◽  
Ellen Gelpi ◽  
Mónica Povedano ◽  
Gabriel Santpere ◽  
Isidro Ferrer
Keyword(s):  
Gene Expression ◽  
Frontal Cortex ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Frontotemporal Lobar Degeneration

scholarly journals The Repressor Element 1-Silencing Transcription Factor Regulates Heart-Specific Gene Expression Using Multiple Chromatin-Modifying Complexes

2007 ◽  
Vol 27 (11) ◽  
pp. 4082-4092 ◽  
Author(s):  
Andrew J. Bingham ◽  
Lezanne Ooi ◽  
Lukasz Kozera ◽  
Edward White ◽  
Ian C. Wood
Keyword(s):  
Gene Expression ◽  
Transcription Factor ◽  
Cardiac Hypertrophy ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Ventricular Myocytes ◽  
Specific Gene ◽  
Histone H4 Acetylation ◽  
Repressor Element

ABSTRACT Cardiac hypertrophy is associated with a dramatic change in the gene expression profile of cardiac myocytes. Many genes important during development of the fetal heart but repressed in the adult tissue are reexpressed, resulting in gross physiological changes that lead to arrhythmias, cardiac failure, and sudden death. One transcription factor thought to be important in repressing the expression of fetal genes in the adult heart is the transcriptional repressor REST (repressor element 1-silencing transcription factor). Although REST has been shown to repress several fetal cardiac genes and inhibition of REST function is sufficient to induce cardiac hypertrophy, the molecular mechanisms employed in this repression are not known. Here we show that continued REST expression prevents increases in the levels of the BNP (Nppb) and ANP (Nppa) genes, encoding brain and atrial natriuretic peptides, in adult rat ventricular myocytes in response to endothelin-1 and that inhibition of REST results in increased expression of these genes in H9c2 cells. Increased expression of Nppb and Nppa correlates with increased histone H4 acetylation and histone H3 lysine 4 methylation of promoter-proximal regions of these genes. Furthermore, using deletions of individual REST repression domains, we show that the combined activities of two domains of REST are required to efficiently repress transcription of the Nppb gene; however, a single repression domain is sufficient to repress the Nppa gene. These data provide some of the first insights into the molecular mechanism that may be important for the changes in gene expression profile seen in cardiac hypertrophy.

scholarly journals Differences in Gene Expression Profile of Primary Tumors in Metastatic and Non-Metastatic Papillary Thyroid Carcinoma—Do They Exist?

2020 ◽  
Vol 21 (13) ◽  
pp. 4629
Author(s):  
Sylwia Szpak-Ulczok ◽  
Aleksandra Pfeifer ◽  
Dagmara Rusinek ◽  
Malgorzata Oczko-Wojciechowska ◽  
Malgorzata Kowalska ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Group Analysis ◽  
Independent Set ◽  
Gene Set Enrichment Analysis ◽  
Papillary Thyroid ◽  
Primary Tumors ◽  
Gene Group

Molecular mechanisms of distant metastases (M1) in papillary thyroid cancer (PTC) are poorly understood. We attempted to analyze the gene expression profile in PTC primary tumors to seek the genes associated with M1 status and characterize their molecular function. One hundred and twenty-three patients, including 36 M1 cases, were subjected to transcriptome oligonucleotide microarray analyses: (set A—U133, set B—HG 1.0 ST) at transcript and gene group level (limma, gene set enrichment analysis (GSEA)). An additional independent set of 63 PTCs, including 9 M1 cases, was used to validate results by qPCR. The analysis on dataset A detected eleven transcripts showing significant differences in expression between metastatic and non-metastatic PTC. These genes were validated on microarray dataset B. The differential expression was positively confirmed for only two genes: IGFBP3, (most significant) and ECM1. However, when analyzed on an independent dataset by qPCR, the IGFBP3 gene showed no differences in expression. Gene group analysis showed differences mainly among immune-related transcripts, indicating the potential influence of tumor immune infiltration or signal within the primary tumor. The differences in gene expression profile between metastatic and non-metastatic PTC, if they exist, are subtle and potentially detectable only in large datasets.

Abstract 17064: Enrichment of Cardiotoxic Gene Expression Profile in Human Induced Pluripotent Stem-Cell Derived Cardiomyocytes in Response to Tyrosine Kinase Inhibitor Nilotinib

Circulation ◽  
2018 ◽  
Vol 138 (Suppl_1) ◽  
Author(s):  
Praful Aggarwal ◽  
Matthew White ◽  
Andrea Matter ◽  
Amy Turner ◽  
Benjamin Olson ◽  
...  
Keyword(s):  
Gene Expression ◽  
Tyrosine Kinase ◽  
Gene Expression Profile ◽  
Cell Lines ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
P Value ◽  
Significant Differential Expression ◽  
Cell Index ◽  
Beat Rate

Small molecule tyrosine kinase inhibitors (TKIs) are a valuable class of therapeutics with widespread clinical utility against multiple cancers. However, there is strong evidence that TKIs are associated with cardiotoxicity and adverse cardiovascular events. Our understanding of the underlying mechanisms related to TKI induced cardiotoxicity is limited. Human iPSC derived cardiomyocytes (hiPSC-CMs) provide a flexible platform and unique model to study the underlying molecular mechanisms associated with TKI associated cardiotoxicity. In this study we describe the gene expression profile between hiPSC-CM cell lines which exhibit susceptibility vs. resistance. RNA-seq analysis was performed in hiPSC-CM cell lines from six participants in the NHLBI HyperGEN study (A to F). Experiments were performed in triplicate using sunitinib (SUN), vandetanib (VAN), gefitinib (GEF) and nilotinib (NIL). We analyzed beat rate, cell index and ATP viability as physiological measurements of CM toxicity and defined a 20% change from the normalized control as TKI susceptibility. Differential gene expression analysis was performed using DESeq2. We observed significant physiological differences between the different hiPSC-CMs after TKI treatment (beat rate, cell index and ATP viability). The most variable cell index and beat rate response was observed for NIL. Based on cell index, lines B, D, E were resistant while A, C, F were significantly more susceptible to NIL. Principal component analysis showed that the variance in gene expression was the highest after NIL treatment when compared to controls (16% for NIL; 11% for VAN; 6% for SUN and 5% for GEF). A total of 567 genes exhibited significant differential expression changes (adj. p-value ≤ 0.1) after NIL treatment in susceptible versus resistant lines. Pathway analysis showed significant enrichment for cardiotoxicity including pathways implicated in cardiac infarction, fibrosis, hypertrophy, and congestive cardiac failure. Taken together, our results identify unique gene expression changes associated with TKI cardiotoxicity. Furthermore, the variability in TKI susceptibility between different hiPSC-CM lines highlights the need to comprehensively assess cardiotoxicity in a diverse set of lines on a physiological and molecular level.

scholarly journals Integration of Gene Expression Profile Data to Verify Hub Genes of Patients with Stanford A Aortic Dissection

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Weitie Wang ◽  
Tiance Wang ◽  
Yong Wang ◽  
Hulin Piao ◽  
Bo Li ◽  
...  
Keyword(s):  
Gene Expression ◽  
Aortic Dissection ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Molecular Mechanisms ◽  
Expression Profiles ◽  
Smooth Muscle Contraction ◽  
Gene Expression Omnibus ◽  
Hub Genes ◽  
Pathogenic Genes

Thoracic aortic dissection (TAD) is a catastrophic disease worldwide, but the pathogenic genes and pathways are largely unclear. This study aims at integrating two gene expression profile datasets and verifying hub genes and pathways involved in TAD as well as exploring potential molecular mechanisms. We will combine our mRNAs expression profile (6 TAD tissues versus 6 non-TAD tissues) and GSE52093 downloaded from the Gene Expression Omnibus (GEO) database. The two mRNAs expression profiles contained 13 TAD aortic tissues and 11 non-TAD tissues. The two expression profile datasets were integrated and we found out coexpression of differentially expressed genes (DEGs) using bioinformatics methods. The gene ontology and pathway enrichment of DEGs were performed by DAVID and Kyoto Encyclopedia of Genes and Genomes online analyses, respectively. The protein-protein interaction networks of the DEGs were constructed according to the data from the STRING database. Cytohubber calculating result shows the top 10 hub genes with CDC20, AURKA, RFC4, MCM4, TYMS, MCM2, DLGAP5, FANCI, BIRC5, and POLE2. Module analysis revealed that TAD was associated with significant pathways including cell cycle, vascular smooth muscle contraction, and adrenergic signaling in cardiomyocytes. The qRT-PCR result showed that the expression levels of all the hub genes were significantly increased in OA samples (p < 0.05), and these candidate genes could be used as potential diagnostic biomarkers and therapeutic targets of TAD.

Effect of chronic lithium treatment on gene expression profile in mouse microglia and brain dendritic cells

2011 ◽  
Vol 71 ◽  
pp. e122
Author(s):  
Zhiqian Yu ◽  
Chiaki Ono ◽  
Yoichiro Tanabe ◽  
Ichiro Sora ◽  
Hiroaki Tomita
Keyword(s):  
Gene Expression ◽  
Dendritic Cells ◽  
Gene Expression Profile ◽  
Expression Profile ◽  
Lithium Treatment
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