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Changes in calcium homeostasis and gene expression implicated in epilepsy in hippocampi of mice overexpressing ORAI1

ABSTRACT: Changes in calcium homeostasis and gene expression implicated in epilepsy in hippocampi of mice overexpressing ORAI1

PROVIDER: PRJNA575645 | ENA |

REPOSITORIES: ENA

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Changes in calcium homeostasis and gene expression implicated in epilepsy in hippocampi of mice overexpressing ORAI1

Project description:We showed that the overexpression of ORAI1 in the neurons of murine brain leads to spontaneous occurrence of seizure-like events in aged animals. We aimed to identify the mechanism responsible for this phenomenon. Using modified Ca2+-addback assay in the slices of CA1 hippocampal region and FURA-2AM calcium indicator we found that overexpression of ORAI1 in neurons leads to altered Ca2+ response. Next, by RNASeq we identified set of genes, whose expression was changed in FVB/NJ-Tg(ORAI1)Ibd mice.

2019-12-17 | GSE138370 | GEO

Changes in Calcium Homeostasis and Gene Expression Implicated in Epilepsy in Hippocampi of Mice Overexpressing ORAI1.

Project description:Previously, we showed that the overexpression of ORAI1 calcium channel in neurons of murine brain led to spontaneous occurrence of seizure-like events in aged animals of transgenic line FVB/NJ-Tg(ORAI1)Ibd (Nencki Institute of Experimental Biology). We aimed to identify the mechanism that is responsible for this phenomenon. Using a modified Ca2+-addback assay in the CA1 region of acute hippocampal slices and FURA-2 acetomethyl ester (AM) Ca2+ indicator, we found that overexpression of ORAI1 in neurons led to altered Ca2+ response. Next, by RNA sequencing (RNAseq) we identified a set of genes, whose expression was changed in our transgenic animals. These data were validated using customized real-time PCR assays and digital droplet PCR (ddPCR) ddPCR. Using real-time PCR, up-regulation of hairy and enhancer of split-5 (Hes-5) gene and down-regulation of aristaless related homeobox (Arx), doublecortin-like kinase 1 (Dclk1), and cyclin-dependent kinase-like 5 (Cdkl5, also known as serine/threonine kinase 9 (Stk9)) genes were found. Digital droplet PCR (ddPCR) analysis revealed down-regulation of Arx. In humans, ARX, DCLK1, and CDLK5 were shown to be mutated in some rare epilepsy-associated disorders. We conclude that the occurrence of seizure-like events in aged mice overexpressing ORAI1 might be due to the down-regulation of Arx, and possibly of Cdkl5 and Dclk1 genes.

| S-EPMC6888010 | biostudies-literature

Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

Project description:A novel model of drug-resistant epilepsy based on the selection of mice treated with phenytoin (PHT) in the 6 Hz seizure model was developed. It leads to the identification of subpopulations of drug-responder and non-responder mice. Transcriptional characterization of the hippocampi from these 2 sub-populations was performed and compared. No significant difference has been observed between the 2 sample groups.

2020-09-11 | GSE157797 | GEO

Transcription profiling of human hippocampi from epilepsy patients with and without hippocampal sclerosis and autopsy controls

Project description:Genome wide gene expression was compared between nonHS, HS temporal lobe epilepsy patients (TLE) and autopsy control hippocampi in a 3-way analysis. In many TLE patients the hippocampus is subject to massive neuronal damage, gliosis and hippocampal sclerosis (HS), while in others there is no apparent hippocampal damage (nonHS). This three way analysis enabled us to differentiate between pathology and epilepsy related processes.

2008-01-01 | E-MEXP-744 | biostudies-arrayexpress

Differential regulation of membrane potential during store-operated calcium entry in neutrophil subsets

Project description:Calcium signals are initiated in immune cells by the process of store-operated calcium entry (SOCE), where receptor activation triggers transient calcium release from the endoplasmic reticulum, followed by opening of plasma membrane calcium-release activated calcium (CRAC) channels. ORAI1, ORAI2 and ORAI3 are known to comprise the CRAC channel, however the contributions of individual isoforms to neutrophil function is not well understood. Here we show that loss of ORAI1 partially decreases calcium influx while loss of both ORAI1 and ORAI2 completely abolishes store-operated calcium entry. In other immune cell types, loss of ORAI2 enhances SOCE. In contrast, we find that ORAI2-deficient neutrophils display decreased calcium influx, which is correlated with measurable differences in regulation of neutrophil membrane potential via KCa3.1. Decreased SOCE in ORAI1-, ORAI2- and ORAI1/2-deficient neutrophils impairs multiple neutrophil functions including phagocytosis, degranulation, leukotriene and ROS production, rendering ORAI1/2-deficient mice highly susceptible to staphylococcal infection. This study demonstrates that ORAI1 and ORAI2 are the primary components of the neutrophil CRAC channel and identifies novel subpopulations of neutrophils where cell membrane potential functions as a rheostat to modulate the SOCE response. These findings have implications for new mechanisms that modulate neutrophil function during infection, acute and chronic inflammatory conditions, and cancer.

2020-09-01 | GSE157200 | GEO

ARX transcription factor implicated in mental retardation and epilepsy

Project description:This SuperSeries is composed of the following subset Series: GSE29985: Identification by ChIP-on-Chip of ARX target genes, a transcription factor implicated in mental retardation and epilepsy GSE30190: Comparison of gene expression between Arx-transfected N2a cells and cells transfected by the corresponding empty vector Refer to individual Series

2011-12-22 | E-GEOD-30191 | biostudies-arrayexpress

Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

Project description:Transcriptional characterization of hippocampi from novel preclinical model of drug-resistant epilepsy

| PRJNA663025 | ENA

RNA Seq Transcriptomic profiling of PDGF-stimulated primary human aortic smooth muscle cells treated with ORAI1 inhibitor relative to controls

Project description:Platelet-derived growth factor (PDGF) signalling and the subsequent activation of the calcium ion channel, ORAI1 are critical drivers of pathological remodelling of native vascular smooth muscle cells to proliferative state, which is a process associated with various vascular diseases. This study aims to reveal transcriptional networks altered following ORAI1 inhibition in vascular smooth muscle cells. To study the effect of ORAI1 inhibition on VSMC biology, we performed RNA-Seq analysis of PDGF-stimulated primary human aortic smooth muscle cells treated with either ORAI1 inhibitor, (n=4) or with vehicle (n=4), and investigated the effect of ORAI1 inhibition on the transcriptional response of cells.

2023-09-21 | E-MTAB-10955 | biostudies-arrayexpress

5-Hydroxymethylcytosine profiling of aging hippocampi

Project description:We profiled 5-hydroxymethylcytosine patterns in hippocampi using hydroxymethylated DNA immunoprecipitation followed by Illumina deep sequencing (hMeDIP-Seq). We profiled the hippocampi of 4 young (3 month old) and 4 aged (18 month old) C57BL/6 mice. Additionally, we profiled the 5-hmC patterns of hippocampi that were stereotactically injected with lentiviral constructs that overexpressed Tet2 or luciferase.

2018-02-25 | GSE102473 | GEO

Project description:Temporal lobe epilepsy (TLE) is the most common subtype of epilepsy in adults and is characterized by neuronal loss, gliosis, and sprouting mossy fibers in the hippocampus. But the mechanism underlying neuronal loss has not been fully elucidated. A new programmed cell death, cuproptosis, has recently been discovered; however, its role in TLE is not clear. To investigate the the features of 12 cuproptosis-related genes in TLEs and controls，six epileptic focus specimens were obtained from the hippocampus of patients diagnosed with intractable TLE according to the International League Against Epilepsy (ILAE) diagnostic criteria (Blümcke et al., 2013). Because the hippocampal specimens from age matched controls were sparse, we only collected two control hippocampi from autopsied individuals without a known history of neurologic or psychiatric disease, ensuring a 3:1 disease-to control match.

2023-06-20 | E-MTAB-13092 | biostudies-arrayexpress

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