Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

β-Hydroxybutyrate Restores Social Deficits via Suppressing HDAC9 in the Anterior Cingulate Cortex of Shank3B-Deficient Mice

ABSTRACT:

Autism spectrum disorder (ASD) is characterized by core deficits in social behavior, yet effective interventions remain limited. Ketogenic diet (KD) shows behavioral benefits in ASD, but the underlying mechanisms remain unclear. Here, using Shank3B knockout (KO) mice, we find that KD induces systemic ketosis with marked elevation of β-hydroxybutyrate (BHB). Oral BHB alone recapitulates KD's prosocial effects, restoring social interaction and neuronal activity in the anterior cingulate cortex (ACC). Mechanistically, we identify HDAC9 as a region- and cell type–specific epigenetic target upregulated in ACC neurons of Shank3B KO mice and suppressed by BHB. HDAC9 overexpression in ACC neurons induces social and synaptic deficits, while class IIa HDAC inhibition phenocopies BHB effects. BHB also restores dendritic complexity, excitatory transmission, and AMPA receptor expression. These findings uncover a metabolite-driven epigenetic mechanism linking ketogenic metabolism to circuit-level rescue of social behavior, highlighting HDAC9 as a therapeutically actionable target for ASD.

INSTRUMENT(S): Liquid Chromatography MS - alternating - reverse-phase

PROVIDER: MTBLS14381 | MetaboLights | 2026-07-08

REPOSITORIES: MetaboLights

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
	a_MTBLS14381_LC-MS_alternating_reverse-phase.txt	Txt
	i_Investigation.txt	Txt
	m_MTBLS14381_LC-MS_alternating_reverse-phase_v2_maf.tsv	Tabular
	s_MTBLS14381.txt	Txt

Items per page:

1 - 4 of 4

Similar Datasets

Transcriptome analysis of Katnal2 knock-out mutant and wild-type mice

Project description:Autism spectrum disorders (ASD) frequently accompany macrocephaly, which could involve hydrocephalic enlargement of brain ventricles. Katnal2 is a microtubule-related protein strongly implicated in ASD. However, it remains unclear whether Katnal2 knockout (KO) in mice leads to microtubule-related cellular deficits and ASD-related phenotypes. We found here that Katnal2-KO mice display social communication deficits, including excessive courtship ultrasonic vocalizations and decreased mating success. Katnal2-KO brains show age-dependent ventricular enlargements and motile ciliary deficits in ependymal cells lining ventricular walls. Katnal2-KO hippocampal neurons, surrounded by lateral ventricles, show limited blood volumes and flow and age-dependent synaptic functional deficits involving synaptic gene downregulation and ASD-like transcriptomic changes. Early postnatal Katnal2 re-expression prevents the ventricular and behavioral phenotypes in Katnal2-KO adults. These results suggest that Katnal2 critically regulates ependymal ciliary function, ventricular volume, CSF circulation, synaptic function, and social communication and that ependymal ciliopathies could underlie ASD-related macrocephaly, ventriculomegaly, and hydrocephalus

2024-03-19 | GSE219228 | GEO

Secretome protein enrichment with click sugars (SPECS) analysis on primary neurons cultured from embryos derived from pregnant mice treated with or without valproic acid

Project description:Autism Spectrum Disorder (ASD) is a developmental disorder characterized by impaired social communication and repetitive behaviors. In recent years, a pharmacological mouse model of ASD involving maternal administration of valproic acid (VPA) has become widely used. Newborn pups in this model show an abnormal balance between excitatory and inhibitory (E/I) signaling in neurons and exhibit ASD-like behavior. To elucidate the molecular basis of this model, we analyzed secretome of primary neurons cultured from embryos maternally treated with or without VPA.

2024-10-26 | PXD042099 | JPOST Repository

Transcriptome analysis of Shank2 mutant mice

Project description:Autism spectrum disorders (ASDs) are a group of developmental disorders that cause variable and heterogeneous phenotypes across three behavioral domains such as atypical social behavior, disrupted communications, and highly restricted and repetitive behaviors. In addition to these core symptoms, other neurological abnormalities are associated with ASD, including intellectual disability (ID). However, the molecular etiology underlying these behavioral heterogeneities in ASD is unclear. Mutations in SHANK2 genes are associated with ASD and ID. Interestingly, two lines of Shank2 knockout mice (e6-7 KO and e7 KO) showed shared and distinct phenotypes. Here, we found that the expression levels of Gabra2, as well as of GABA receptor-mediated inhibitory neurotransmission, are reduced in Shank2 e6-7, but not in e7 KO mice compared with their own wild type littermates. Furthermore, treatment of Shank2 e6-7 KO mice with an allosteric modulator for the GABAA receptor reverses spatial memory deficits, indicating that reduced inhibitory neurotransmission may cause memory deficits in Shank2 e6-7 KO mice. This article is part of the Special Issue entitled 'Ionotropic glutamate receptors'.

2017-01-24 | GSE79824 | GEO

Acetate supplementation rescues social deficits and alters transcriptional regulation in prefrontal cortex of Shank3 deficient mice

Project description:Autism spectrum disorder (ASD) is a heterogenous neurodevelopmental disorder with complex pathophysiology including both genetic and environmental factors. Recent evidence demonstrates the gut microbiome and its resultant metabolome can influence brain and behavior and have been implicated in ASD. To investigate gene by microbiome interactions in a model for genetic risk of ASD, we utilize mutant mice carrying a deletion of the ASD-associated Shank3 gene (Shank3KO). Shank3KO have altered microbiome composition and function at baseline in addition to social deficits. Further depletion of the microbiome with antibiotics exacerbates social deficits in Shank3KO, and results in transcriptional changes in the frontal cortex. Supplementation with the microbial metabolite acetate leads to reversal of social behavioral phenotypes even in mice with a depleted microbiome, and significantly alters transcriptional regulation in the prefrontal cortex. These results suggest a key role for the gut microbiome and the neuroactive metabolite acetate in regulating ASD-like behaviors.

2023-03-02 | GSE225983 | GEO

Endothelial SHANK3 Regulates Tight Junctions in the Neonatal Blood-Brain Barrier through β-Catenin Signaling

Project description:Autism spectrum disorder (ASD) is a neurodevelopmental condition caused by a combination of genetic and environmental factors. The blood-brain barrier (BBB) plays a key role in regulating environmental influences on the brain, yet its contributions to ASD remain unclear. We report that endothelium-specific SHANK3 (eSHANK3) is expressed in brain endothelial cells (BECs) that form the BBB. Our analysis of eSHANK3 interactions in BECs shows significant enrichment of proteins involved in membrane and cell junction functions. We found that eSHANK3 maintains tight junction (TJ) integrity, which is essential for BBB function. Loss of Shank3 disrupts TJs, increasing paracellular passage through the endothelium. In vivo, eShank3 knockout (KO) mice show BBB hyperpermeability, reduced neuronal excitability, and impaired ultrasonic communication. Although BBB permeability is restored in adulthood, the mutant mice continue to have reduced neuronal excitability and impaired sociability. Further analysis reveals that neonatal BBB hyperpermeability is due to β-Catenin imbalance caused by eShank3-KO. Restoring β-Catenin signaling rescues neuronal and social behavior deficits. These findings uncover a new pathogenic mechanism linked to Shank3 in ASD and suggest that neonatal BECs in the BBB could be a potential therapeutic target for ASD.

2025-02-07 | PXD059466 | Pride

Quantitative Proteomics of Dorsolateral Prefrontal Cortex

Project description:Autism spectrum disorder (ASD) is a severe neurodevelopmental disorder with a rising prevalence and genetic and environmental etiologies. Symptoms include deficits in social communication, repetitive patterns of behavior, and cognitive impairment. Neuroanatomic and biochemical investigations involve many brain areas with imbalance between glutamatergic and inhibitory neurotransmitters. We hypothesized that investigation of the synaptic compartment of the dorsolateral prefrontal cortex may provide proteomics signatures that may identify the biological underpinnings of cognitive deficits in childhood ASD. Subcellular fractionation of the synaptoneurosomes from Brodmann area 9 of a well- characterized age- and postmortem-interval-matched samples from children and adults with idiopathic ASD vs. healthy controls, were subjected to HPLC–tandem mass spectrometry and proteomic analysis.

2025-05-06 | PXD048017 | Pride

CDH11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit

Project description:The molecular etiology of numerous risk genes for autism spectrum disorder (ASD), including CDH11, remains elusive. We investigated the role of CDH11 in the development of ASD-related behaviors using gene-deficient mice. CDH11 is enriched at synapses in glutamatergic neurons of the anterior cingulate cortex (ACC), which project to the striatum, nucleus accumbens, and amygdala. Ablation of Cdh11 in these neurons during development increases self-grooming and reduces sociability, with decreased neuronal activity in the ACC. Chemogenetic inhibition of ACC glutamatergic neurons recapitulates the over-grooming phenotype, while activation of these neurons mitigates self-grooming in Cdh11-deficient mice. Proteomics of ACC synaptosomes and CDH11 interactomes suggest the involvement of CDH11 in synaptic vesicle trafficking, supported by reduced presynaptic vesicle density at excitatory synapses in Cdh11-deficient mice. These findings highlight the critical role of CDH11 in ASD-related brain circuit development and offer insights into the molecular mechanisms and potential therapeutic targets for ASD.

2025-08-08 | PXD055834 | Pride

CDH11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit

2025-08-08 | PXD056411 | Pride

CDH11 regulates presynaptic vesicle trafficking and neuronal activity in autism-related brain circuit

2025-08-08 | PXD056074 | Pride

Moesin deficiency leads to microglia-mediated synaptic pruning and social abnormality: a post-GWAS functional genomics study

Project description:Genome-wide association studies (GWAS) implicated a noncoding antisense RNA designated as MSNP1AS in susceptibility to autism spectrum disorders (ASD). MSNP1AS binds to and downregulates the Moesin (MSN) transcript and is highly overexpressed in postmortem cerebral cortex of individuals with ASDs. However, the mechanistic link between Moesin loss in vivo and ASD-related phenotypic traits remains enigmatic. Here, we generated Moesin knockout (Msn KO) mice, on which neurobehavioral tests revealed impaired social novelty and repetitive behaviors. Single-cell transcriptomics and electrophysiology recording indicated activated status of the microglia, leading to aberrant C1q-dependent synaptic pruning followed by synaptic deficits in medial prefrontal cortex in KO mice. Aberrant regulatory pathway from sequencing data guided us to block type I interferon pathway by IFNAR1 blocking antibody via nasal administration, which rescued microglial abnormalities and social deficits in Msn KO mice. Taken together, Moesin mediates interferon signaling and synaptic pruning to affect ASD-like behaviors, providing a functional genetic link between MSN and neurobehavioral abnormalities.

2025-06-11 | GSE293405 | 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