Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

NPAS3-regulated astrocyte mitochondria bioenergetics is required for cognition

ABSTRACT: The basic helix-loop-helix (bHLH) transcription factor neuronal PAS domain protein 3 (NPAS3) provides transcriptional regulation of metabolic pathways, and despite its name is highly expressed in astrocytes. NPAS3 variants have been associated with cognitive dysfunction in several neuropsychiatric conditions, but the underlying brain cell type-specific mechanisms remain obscure. Here, we report that NPAS3 is a key regulator of mitochondria bioenergetics in astrocytes. Selective deletion of Npas3 in mature murine astrocytes decreases expression of Slc25a18 and its protein product, mitochondrial glutamate carrier 2, leading to reduced oxidative phosphorylation and lactate production in astrocytes. This deficit subsequently causes reduced excitability, dendritic spine density, and dendritic arborization of medial prefrontal cortex pyramidal neurons. Mice with Npas3-deficient cortical astrocytes exhibit impaired trace fear conditioning, which is rescued by lactate treatment. Thus, the present study demonstrates a mechanistic link between NPAS3-dependent astrocyte mitochondria bioenergetics and cognitive function and provides insights for glia-targeting treatment of cognitive dysfunction in neuropsychiatric disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE274921 | GEO | 2026/05/04

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Identification of NPAS3 cistrome in the mouse cortical astrocytes (DIV 14).

Project description:Genome-wide binding sites of NPAS3 were identified in mouse cortical astrocytes (DIV 14).

2022-07-19 | GSE179592 | GEO

The LncRNA 3222401L13Rik Is Upregulated in Aging Astrocytes and Regulates Neuronal Support Function Through Interaction with Npas3

Project description:Aging is linked to a decline in cognitive functions and significantly increases the risk of neurodegenerative diseases. While molecular changes in all central nervous system (CNS) cell types contribute to aging-related cognitive decline, the mechanisms driving disease development or offering protection remain poorly understood. Long non-coding RNAs (lncRNAs) have emerged as key regulators of cellular functions and gene expression, yet their roles in aging, particularly within glial cells, are not well characterized. In this study, we investigated lncRNA expression profiles in non-neuronal cells from aged mice. We identified 3222401L13Rik, a previously unstudied lncRNA enriched in glial cells, as being specifically upregulated in astrocytes during aging. Knockdown of 3222401L13Rik in primary astrocytes revealed its critical role in regulating genes essential for neuronal support and synapse organization. This function was also conserved in human iPSC-derived astrocytes. Additionally, we found that 3222401L13Rik mediates its cellular effects through interaction with the transcription factor Neuronal PAS Domain Protein 3 (Npas3), and that overexpression of Npas3 effectively rescued the functional deficits observed in astrocytes lacking 3222401L13Rik. Our findings suggest that upregulation of 3222401L13Rik in aging astrocytes acts as a compensatory mechanism to enhance neuronal and synaptic support, potentially delaying the onset of molecular and structural changes in both astrocytes and neurons. Strategies to boost 3222401L13Rik expression earlier in life may help mitigate age-associated loss of neuronal plasticity.

2025-01-06 | GSE275168 | GEO

The LncRNA 3222401L13Rik Is Upregulated in Aging Astrocytes and Regulates Neuronal Support Function Through Interaction with Npas3 [young]

2026-01-12 | GSE286099 | GEO

NPAS3-HEK293-standardcond-Illumina

Project description:NPAS3 or truncated NPAS3 overexpressed HEK293 cells or control HEK293 cells were collected at 24 hours after gene overexpression.Total RNA from alll samples was extracted.Biotinylated cRNA was prepared using the Illumina total Prep RNA application Kits.Hybridization, washing and scanning were performed according to the Illumina BeadStation 500* manual (revision C)

2011-10-03 | E-TABM-1078 | biostudies-arrayexpress

Whole transcriptome sequencing of Npas3+/- and WT cortex at P0 stage

Project description:Purpose: To gain insight into the impact of NPAS3 deficiency on astrogenesis in mice, RNA-seq was used to analyze the genome-wide changes resulting from Npas3+/- and WT cortex at P0 stage. Methods: Total RNA was extracted from Npas3+/- and WT cortex at P0 stage. Then, total RNA was quantified and quality controlled by Agilent Bioanalyzer 2100 system. After cDNA library construction, the library preparations were sequenced on an Illumina NovaSeq 6000 platform in Novogene. Results: At significance cutoffs corresponding to FDR < 0.05, a total of 625 DEGs were identified in Npas3+/- mice. Conclusions: Our results show that Npas3+/- mice exhibit defective astrogenesis and abnormal synapse function.

2022-07-19 | GSE179608 | GEO

Identification of NPAS3 cistrome in the mouse cortical astrocytes (DIV 14).

Project description:Identification of NPAS3 cistrome in the mouse cortical astrocytes (DIV 14).

| PRJNA744243 | ENA

Activity-dependent neuronal Klotho enhances astrocytic aerobic glycolysis

Project description:Mutations of the β-glucuronidase protein α-Klotho have been associated with premature aging, and altered cognitive function. Although highly expressed in specific areas of the brain, Klotho functions in the central nervous system remain unknow. Here, we show that cultured hippocampal neurons respond to insulin and glutamate stimulation by elevating Klotho protein levels. Conversely, AMPA and NMDA antagonism suppress neuronal Klotho expression. We also provide evidence that soluble Klotho enhances astrocytic aerobic glycolysis by hindering pyruvate metabolism through the mitochondria, and stimulating its processing by lactate dehydrogenase. Pharmacological inhibition of FGFR1, Erk phosphorylation, and monocarboxylic acid transporters prevents Klotho-induced lactate release from astrocytes. Taken together these data suggest Klotho is a potential new player in the metabolic coupling between neurons and astrocytes. Neuronal glutamatergic activity and insulin modulation elicit Klotho release, which in turn stimulates astrocytic lactate formation and release. Lactate can then be used by neurons as a metabolic substrate contributing to fulfill their elevated energy requirements.

2018-03-08 | GSE100046 | GEO

Whole transcriptome sequencing of mouse cortical astrocytes (DIV 14).

Project description:To gain futher insight into the Npas3 regulatory network in astrocytes, RNA-seq was used to analyze the genome-wide changes resulting from the days in vitro (DIV) 14 astrocytes of P0 wild-type (WT) mice and littermate NPAS3-/- mice. Total RNA was extracted from DIV 14 astrocytes of P0 Npas3-/- and WT mice. Then, total RNA was quantiﬁed and quality controlled by Agilent Bioanalyzer 2100 system. After cDNA library construction, the library preparations were sequenced on an Illumina NovaSeq 6000 platform in Novogene.

2022-07-19 | GSE179602 | GEO

NPAS3-HEK293-circadian-Illumina

Project description:The fragments of FLNPAS3 and DeltaNPAS3 were transferred into a similar TET-inducible expression plasmid and transfected into HEK293 [T-REx-293] cells (Invitrogen). At the zero hour time-point, cells were shifted into a serum-rich medium plus tetracycline in order to induce circadian cycling and NPAS3 overexpression. Parental HEK293 [T-REx-293] cells after circadian rhythmcity induction for +12hr/+24hrs were used as negative controls because stably integrated FLNPAS3/DeltaNPAS3 cell lines showed a low level of leaky transcription in the absence of tetracycline. At +2 hours, cells were washed with DMEM and then incubated with the same plus tetracycline for the remaining period of the experiment. Cell samples were collected at +12hrs and +24hrs respectively. For all circadian cell culture experiments with FLNPAS3/DeltaNPAS3/parental negative control cell lines, duplicate biological samples were assessed. Microarray probes synthesised from RNA extraction products was quantified using an Agilent Bioanalyzer to ensure high quality probes of equal quantity between experiments. Sentrix® HumanRef-8 v2 chips were used to detect gene expression profiles.

2011-10-03 | E-TABM-1079 | biostudies-arrayexpress

Pharmacological inhibition of mitochondrial soluble adenylyl cyclase in astrocytes causes activation of AMP-activated protein kinase and induces breakdown of glycogen

Project description:Astrocytes contain the majority of the brain’s supply of glycogen which has been suggested to play an important role in neuronal synaptic plasticity. This may be mediated by release of glycogen-derived lactate or glutamine supporting neuronal metabolism or via induction of neuronal signaling pathways. The second messenger cyclic AMP (cAMP) can induce glycogen breakdown and activation of cytosolic soluble adenylyl cyclase (sAC) in astrocytes has been suggested to be the link between neuronal depolarization and glycogen breakdown. However, recent studies have revealed that sAC residing in the mitochondria rather than the cytosol is regulating mitochondrial bioenergetics, and that employing pharmacological inhibitors of sAC significantly alters cellular energy metabolism. This effect on energy metabolism could influence the interpretation of previous studies employing pharmacological inhibition of sAC. Here, we show that pharmacological inhibition of sAC lowers mitochondrial respiration, induces phosphorylation of the metabolic master switch AMPK, and decreases glycogen stores in cultured astrocytes. In light of this, we discuss the pharmacological challenges of investigating the functional and metabolic roles of sAC in astrocytes.

2021-08-13 | PXD027901 | 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