PXD076235-1

PXD076235 is an original dataset announced via ProteomeXchange.

Title	Pathologically activated GABAA α3 receptors underlie autism-like features
Description	Social deficits and repetitive behaviors define autism spectrum disorder (ASD), yet their shared underlying mechanisms remain elusive. Here we uncover a convergent pathophysiological mechanism across multiple ASD models. We found that GABAergic neurons in the dorsal raphe nucleus (DRNGABA neurons) are hyperactive in Shank3B–/– mice. Chemogenetic activation of these neurons recapitulated ASD-like behaviors, whereas inhibition reversed them. Shank3 knockdown in DRNGABA neurons phenocopied ASD-related changes through upregulation of ErbB4-mGluR1/5 signaling. Sustained DRNGABA hyperactivity drove the pathological recruitment of postsynaptic GABAA α3 receptors, resulting in hypoactivity of DRN5-HT neurons. Gabra3 knockdown in DRN5-HT neurons rescued behavioral deficits in Shank3B–/– mice. Notably, systemic low-dose bicuculline—selectively inhibiting GABAA α3 receptors—ameliorated core ASD-like behaviors across multiple etiologically distinct models, including Shank3B–/– mice, offspring of Poly: IC-injected dams, and BTBR mice, without affecting basal transmission. Together, these findings identify pathologically activated GABAA α3 receptors as a convergent therapeutic target for ASD.
HostingRepository	iProX
AnnounceDate	2026-03-27
AnnouncementXML	Submission_2026-03-27_02:14:12.907.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	Yuan Zhang
SpeciesList	scientific name: Mus musculus; NCBI TaxID: 10090;
ModificationList	No PTMs are included in the dataset
Instrument	Orbitrap Fusion

Revision	Datetime	Status	ChangeLog Entry
0	2026-03-27 02:13:55	ID requested
⏵ 1	2026-03-27 02:14:13	announced

Dataset with its publication pending

submitter keyword: Autism spectrum disorder, the dorsal raphe nucleus, GABAergic neurons, GABAA α3 receptors, Pathologically activated

Xinhong Zhu
contact affiliation	Pazhou Laboratory
contact email	zhuxh527@126.com
lab head
Yuan Zhang
contact affiliation	Pazhou Laboratory
contact email	bolanzy@163.com
dataset submitter

iProX dataset URI