Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Stra8, an Activity-Dependent Modulator of Neural Circuit, Safeguards Neuronal Integrity

ABSTRACT: While neuronal activity is essential for brain function, it inherently threatens neurons and impairs neuronal integrity1. Here we show that activity-induced expression of Stra8 (stimulated by retinoic acid gene 8) plays a crucial role in protecting neuronal integrity. To date, Stra8 has been considered as germline-specific2, and its role in somatic cells has not been explored. Our results show that Stra8 is expressed in the adult mouse brain. Neuronal activity (i.e., exploration of a novel environment) induced Stra8 expression, and this process is mediated by calcium influx and depolarization through NMDA-type glutamate receptors. Importantly, neuron-specific knockout of Stra8 induced multifaceted features of neuronal degeneration in young adult mice, including accumulation of DNA damage, impaired proteostasis, heightened inflammation, nuclear membrane erosion, decreased dendritic plasticity, as well as impaired learning and memory and increased vulnerability to kainic acid-induced excitotoxicity. Additionally, electrophysiology studies show that loss of Stra8 compromises inhibitory neural circuity and function. Mechanistically, Stra8 binds to the regulatory sequences of neuromodulator genes and regulates their expression, among which loss of Stra8 results in an upregulated expression of Npas4; however, aberrantly expressed Npas4 protein is confined to the nuclear periphery in neurons. Together, these findings establish Stra8 as an activity-dependent modulator of neural circuitry that protects neuronal integrity.

ORGANISM(S): Mus musculus

PROVIDER: GSE274976 | GEO | 2025/10/03

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Stra8, an Activity-Dependent Modulator of Neural Circuit, Safeguards Neuronal Integrity

Project description:Stra8, an Activity-Dependent Modulator of Neural Circuit, Safeguards Neuronal Integrity

| PRJNA1148663 | ENA

Global gene expression comparation among testes, ovaries, Smad4flox/floxMerCreMer Stra8+/− ovaries and Smad4flox/floxMerCreMer Stra8−/− ovaries

Project description:To confirm that female-to-male sexual fate reversal in Smad4flox/floxMerCreMer Stra8−/− ovaries occurs independently of somatic environment. We analyzed transcriptome of samples using RNA from control testes, ovaries, Smad4flox/floxMerCreMer Stra8+/− and Smad4flox/floxMerCreMer Stra8−/− ovaries.

2016-05-11 | GSE68773 | GEO

mRNA-Seq profiling of Stra8-deficient and wild-type testes

Project description:We sequenced mRNA in grossly enlarged testes from 1-year-old Stra8-deficient mice, and in testes from adult male wild-type controls, to verify that Stra8-deficient testes are enriched for genes normally expressed in type A spermatogonia. Examination of mRNA levels in 6 whole-testis samples (3 replicates of each genotype). Specifically, we sequenced mRNA in grossly enlarged testes from three 1-year-old Stra8-deficient male mice, and in normal testes from three adult male wild-type controls

2015-04-03 | E-GEOD-67169 | biostudies-arrayexpress

An NPAS4:NuA4 complex couples synaptic activity to DNA repair

Project description:Neuronal activity is critical for adaptive circuit remodeling but poses an inherent risk to the stability of the genome across the long lifespan of post-mitotic neurons1-5. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is not known. Here we identify an activity-dependent DNA repair mechanism via a new form of the NuA4/TIP60 chromatin modifier that assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex directly from the brain and demonstrate its functions in eliciting activity-dependent changes to neuronal transcriptomes and circuitry. By identifying the landscape of activity-induced DNA double-strand breaks in the brain, we show that the NPAS4:NuA4 complex binds to recurrently damaged regulatory elements and recruits additional DNA repair machinery to stimulate their repair. Gene regulatory elements bound by the NPAS4:NuA4 complex are partially protected from age-dependent accumulation of somatic mutations. Impaired NPAS4:NuA4 signaling leads to a cascade of cellular defects including dysregulated transcriptional responses to activity, loss of control over neuronal inhibition, and genome instability, culminating in reduced organismal lifespan. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental disorders and autism. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation and whose disruption may contribute to developmental disorders, neurodegeneration and aging.

2023-02-15 | PXD038718 | Pride

ChIP-seq of Stra8-Bound Genomic Regions in Mouse Hippocampus

Project description:We performed ChIP-seq for Stra8 in the hippocampus of Stra8-AVI mice using the Illumina NovaSeq 6000 sequencing platform.

2025-10-03 | GSE304128 | GEO

Mus musculus Stra8-deficient fetal ovary transcriptome

Project description:Identification of the mouse embryonic germ cell Stra8-/- transcriptome

2015-08-13 | GSE70359 | GEO

Roles of Stra8 and Tcerg1l in retinoic acid induced spermatogonial differentiation in mouse.

Project description:Retinoic acid (RA) induces spermatogonial differentiation, but the mechanism by which it operates remains largely unknown. We developed a germ cell culture assay system to study genes involved in spermatogonial differentiation triggered by RA. Stimulated by Retinoic Acid 8 (Stra8), an RA-inducible gene, is indispensable for meiosis initiation, and its deletion results in a complete block of spermatogenesis at the pre-leptotene/zygotene stage due to failure to complete pre-meiotic DNA replication. To interrogate the role of Stra8 in RA mediated differentiation of spermatogonia, we derived germ cell cultures from the neonatal testis of both wild type and Stra8 knock-out mice. We provide the first evidence that Stra8 plays a crucial role in modulating the responsiveness of undifferentiated spermatogonia to RA and facilitates transition to a differentiated state. Stra8-mediated differentiation is achieved through downregulation of a large portfolio of genes and pathways, most notably including genes involved in the spermatogonial stem cell self-renewal process. We also report here for the first time the role of Transcription Elongation Regulator-1 Like (Tcerg1l) as a downstream effector of RA-induced spermatogonial differentiation.

2021-05-05 | GSE173873 | GEO

mRNA-Seq profiling of Stra8-deficient and wild-type testes

2015-04-03 | GSE67169 | GEO

Single-nucleus transcriptome of the hippocampus from Stra8-cKO (Stra8L/-; Nestin-Cre) mice

Project description:We performed single-nucleus RNA sequencing (snRNA-seq) of the hippocampus from Stra8-cKO mice using the 10x Genomics Chromium platform to investigate the effects of Stra8 loss.

2025-10-03 | GSE304116 | GEO

An NPAS4:NuA4 complex couples synaptic activity to DNA repair [RNA-seq]

Project description:Neuronal activity is critical for adaptive circuit remodeling but poses an inherent risk to the stability of the genome across the long lifespan of post-mitotic neurons. Whether neurons have acquired specialized genome protection mechanisms that enable them to withstand decades of potentially damaging stimuli during periods of heightened activity is not known. Here we identify the first example of a neuronal-specific DNA repair mechanism via a new form of the NuA4/TIP60 chromatin modifier that assembles in activated neurons around the inducible, neuronal-specific transcription factor NPAS4. We purify this complex directly from the brain and demonstrate its function in eliciting activity-dependent changes to neuronal transcriptomes and neuronal circuitry. NPAS4:NuA4 binds at fragile regulatory regions that undergo neuronal activity-induced DNA double-strand breaks and recruits additional DNA repair machinery to stimulate the repair of these sites. Gene regulatory elements bound by the NPAS4:NuA4 complex are partially protected from age-dependent accumulation of somatic mutations. Impaired NPAS4:NuA4 signaling leads to a cascade of cellular defects including dysregulated transcriptional responses to activity, loss of control over neuronal inhibition, and genome instability, culminating in reduced longevity at the organismal level. In addition, mutations in several components of the NuA4 complex are reported to lead to neurodevelopmental disorders and autism. Together, these findings identify a neuronal-specific complex that couples neuronal activity directly to genome preservation and whose disruption may contribute to developmental disorders, neurodegeneration and aging.

2022-12-16 | GSE175964 | GEO

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