Counterbalancing O-GlcNAcylation and STAT3 Phosphorylation in Ventral Tegmental Area Dopaminergic Neurons Mediates Behavioral Adaptations to Acute Restraint Stress.

ABSTRACT: Acute stressors, significant risk factors for mood disorders, increase anxiety and reduce reward sensitivity. However, the underlying neuroadaptive mechanisms remain unclear. Here, it is shown that acute restraint stress upregulates Signal Transducer and Activator of Transcription 3 (STAT3) signaling and O-GlcNAcylation in ventral tegmental area (VTA) dopaminergic (DAergic) neurons. Multi-omics analyses in O-linked N-acetylglucosamine transferase (OGT) conditional knockout (cKO) mice reveal a counterbalancing mechanism between O-GlcNAcylation and STAT3^Ser727 phosphorylation. In vivo fiber-optic recordings and behavioral experiments demonstrate that STAT3^Ser727 phosphorylation mediates the suppression of DAergic neuronal activity and reward sensitivity, as well as the

SUBMITTER: Shao M 

PROVIDER: S-EPMC12533289 | biostudies-literature | 2025 Oct

REPOSITORIES: biostudies-literature