Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Neurodevelopmental ATM deficiency affects glutamatergic transmission through KCC2-KARs expression in the hippocampus but not in the cortex

ABSTRACT: Neurodevelopmental ATM deficiency affects glutamatergic transmission through KCC2-KARs expression in the hippocampus but not in the cortex

PROVIDER: PRJNA835074 | ENA |

REPOSITORIES: ENA

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	SRR19084121_1.fastq.gz	Fastqsanger.gz
	SRR19084121_2.fastq.gz	Fastqsanger.gz
	SRR19084122_1.fastq.gz	Fastqsanger.gz
	SRR19084122_2.fastq.gz	Fastqsanger.gz
	SRR19084123_1.fastq.gz	Fastqsanger.gz

Items per page:

1 - 5 of 16

Similar Datasets

Neurodevelopmental ATM deficiency affects glutamatergic transmission through KCC2-KARs expression in the hippocampus but not in the cortex

Project description:Interest in the function of ataxia-telangiectasia mutated protein (ATM) is extensively growing as evidenced by preclinical studies which continuously associate ATM loss with new intracellular pathways. To further investigate ATM involvement in neurotransmission, we initially exploited ATM+/- and ATM-/- mice. ATM defective animals display cognitive defects rescued by the delivery of the antidepressant Fluoxetine (Fluox). Prenatal Fluox increases levels of the chloride intruder NKCC1, previously described lowered in ATM defective mice. Surprisingly, this result occurs exclusively at hippocampal level suggesting an ATM context-specificity. Indeed, a deeper investigation of excitatory synapses revealed increased Gluk1 and Gluk5 subunit-containing kainate receptors (KARs) levels in the hippocampus, but not cortex, of ATM+/- and ATM-/- mice. The comparable composition between wt and ATM+/- post-synapses (TIF purification) suggests a presynaptic KARs localization and in vitro and in ex vivo electrophysiology that KARs are fully active. Since KAR subunits functionally interact with the chloride cotransporter KCC2, which is highly expressed in ATM deficient mice, we blocked KCC2 activity during the development of ATM+/- cultures and found reduced KARs levels. Conversely, the transient and acute blockade of ATM kinase activity achieved by KU55933 in adults does not move similar changes as indicated by a completely different panel of deregulated genes identified in RNA-seq investigation performed on hippocampi explanted from KU mice. Our data, indicating that such alterations are developmental regulated and linked to ATM kinase activity through the KCC2 regulation, add new findings useful for a deeper understanding of ATM function in central neurons. Importantly, controlling the KCC2/NKCC1 levels, ATM affects both the GABAergic and glutamatergic system in the hippocampus.

2022-07-05 | GSE202217 | GEO

ATM rules neurodevelopment and glutamatergic transmission in the hippocampus but not in the cortex.

Project description:Interest in the function of ataxia-telangiectasia-mutated protein (ATM) is extensively growing as evidenced by preclinical studies that continuously link ATM with new intracellular pathways. Here, we exploited Atm+/- and Atm-/- mice and demonstrate that cognitive defects are rescued by the delivery of the antidepressant Fluoxetine (Fluox). Fluox increases levels of the chloride intruder NKCC1 exclusively at hippocampal level suggesting an ATM context-specificity. A deeper investigation of synaptic composition unveils increased Gluk-1 and Gluk-5 subunit-containing kainate receptors (KARs) levels in the hippocampus, but not in the cortex, of Atm+/- and Atm-/- mice. Analysis of postsynaptic fractions and confocal studies indicates that KARs are presynaptic while in vitro and ex vivo electrophysiology that are fully active. These changes are (i) linked to KCC2 activity, as the KCC2 blockade in Atm+/- developing neurons results in reduced KARs levels and (ii) developmental regulated. Indeed, the pharmacological inhibition of ATM kinase in adults produces different changes as identified by RNA-seq investigation. Our data display how ATM affects both inhibitory and excitatory neurotransmission, extending its role to a variety of neurological and psychiatric disorders.

| S-EPMC9288428 | biostudies-literature

Phosphorylation of 53BP1 by ATM enforce neurodevelopmental programs in cortical organoids

Project description:Phosphorylation of 53BP1 by ATM enforce neurodevelopmental programs in cortical organoids

| PRJNA963212 | ENA

Phosphorylation of 53BP1 by ATM enforce neurodevelopmental programs in cortical organoids

Project description:53BP1 is a well-established DNA damage repair factor that has recently been shown to regulate gene expression and critically influence tumor suppression and neural development. For gene regulation, how 53BP1 is regulated remains unclear. Here, we showed that 53BP1-serine 25 phosphorylation by ATM is required for neural progenitor cell proliferation and neuronal differentiation in cortical organoids. 53BP1-serine 25 phosphorylation dynamics controls 53BP1 target genes for neuronal differentiation and function, cellular response to stress, and apoptosis. Beyond 53BP1, ATM is required for phosphorylation of factors in neuronal differentiation, cytoskeleton, p53 regulation, and ATM, BNDF, and WNT signaling pathways for cortical organoid differentiation. Overall, our data suggest that 53BP1 and ATM control key genetic programs required for human cortical development.

2024-08-11 | GSE231321 | GEO

Maternal Adiposity Alters Transcriptomic and Epigenomic Neurodevelopmental Landscapes in the Fetal Hippocampus

Project description:Maternal Adiposity Alters Transcriptomic and Epigenomic Neurodevelopmental Landscapes in the Fetal Hippocampus

| PRJNA977655 | ENA

Panicum virgatum strain:ATM | cultivar:ATM

Project description:Panicum virgatum ATM Resequencing genome sequencing

| PRJNA332580 | ENA

Maternal Adiposity Alters Transcriptomic and Epigenomic Neurodevelopmental Landscapes in the Fetal Hippocampus (Bisulfite-Seq)

Project description:Maternal Adiposity Alters Transcriptomic and Epigenomic Neurodevelopmental Landscapes in the Fetal Hippocampus (Bisulfite-Seq)

| PRJNA977657 | ENA

Maternal Adiposity Alters Transcriptomic and Epigenomic Neurodevelopmental Landscapes in the Fetal Hippocampus (RNA-Seq)

Project description:Maternal Adiposity Alters Transcriptomic and Epigenomic Neurodevelopmental Landscapes in the Fetal Hippocampus (RNA-Seq)

| PRJNA977660 | ENA

Social isolation-induced transcriptomic changes in mouse hippocampus impact the synapse and show convergence with human genetic risk for neurodevelopmental phenotypes

Project description:Early life stress (ELS) can impact brain development and is a risk factor for neurodevelopmental disorders such as schizophrenia. Post-weaning social isolation (SI) is used to model ELS in animals, using isolation stress to disrupt a normal developmental trajectory. We aimed to investigate how SI affects the expression of genes in mouse hippocampus and to investigate how these changes related to the genetic basis of neurodevelopmental phenotypes. BL/6J mice were exposed to post-weaning SI (PD21-25) or treated as group-housed controls (n = 7-8 per group). RNA sequencing was performed on tissue samples from the hippocampus of adult male and female mice. Four hundred and 1,215 differentially-expressed genes (DEGs) at a false discovery rate of < 0.05 were detected between SI and control samples for males and females respectively. DEGS for both males and females were significantly overrepresented in gene ontologies related to synaptic structure and function, especially the post-synapse. DEGs were enriched for common variant (SNP) heritability in humans that contributes to risk of neuropsychiatric disorders (schizophrenia, bipolar disorder) and to cognitive function. DEGs were also enriched for genes harbouring rare de novo variants that contribute to autism spectrum disorder and other developmental disorders. Finally, cell type analysis revealed populations of hippocampal astrocytes that were enriched for DEGs, indicating effects in these cell types as well as neurons. Overall, these data suggest a convergence between genes dysregulated by the SI stressor in the mouse and genes associated with neurodevelopmental disorders and cognitive phenotypes in humans.

2023-11-02 | GSE246551 | GEO

Modulation of proteostasis counteracts oxidative stress and affects DNA base excision repair capacity in ATM-deficient cells

Project description:Ataxia telangiectasia (A-T) is a syndrome associated with loss of ATM protein function. Neurodegeneration and cancer predisposition, both hallmarks of A-T, are likely to emerge as a consequence of the persistent oxidative stress and DNA damage observed in this disease. Surprisingly however, despite these severe features, a lack of functional ATM is still compatible with early life, suggesting that adaptation mechanisms contributing to cell survival must be in place. Here we address this gap in our knowledge by analysing the process of human fibroblast adaptation to the lack of ATM. We identify profound rearrangement in cellular proteostasis occurring very early on after loss of ATM in order to counter protein damage originating from oxidative stress. Change in proteostasis, however, is not without repercussions. Modulating protein turnover in ATM-depleted cells also has an adverse effect on the DNA base excision repair pathway, the major DNA repair system that deals with oxidative DNA damage. As a consequence, the burden of unrepaired endogenous DNA lesions intensifies, progressively leading to genomic instability. Our study provides a glimpse at the cellular consequences of loss of ATM and highlights a previously overlooked role for proteostasis in maintaining cell survival in the absence of ATM function.

2017-09-04 | PXD006648 | Pride

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data