Glucosylceramide regulates depression through activating peroxisome proliferator-activated receptor gamma in dorsal striatum.

ABSTRACT: Rationale: Depression is a heterogeneous disorder influenced by cell type-specific gene transcription in the brain. Peroxisome proliferator-activated receptor gamma (PPARγ) plays an important role in modulating the pathophysiology of depression. However, the role of PPARγ signaling in modulating depression-responsive neuronal ensembles remains largely unknown. Methods: We established a chronic restraint stress mouse model and integrated multi-omics and functional approaches to investigate the role of glucosylceramide (GlcCer)-PPARγ signaling in stress-induced depression. Conditional knockout mice targeting glucosylceramide synthase (GCS) or Pparg in dopamine D2 receptor-expressing medium spiny neurons (D2-MSNs) were generated using a Cre-loxP system, and molecular assa

SUBMITTER: Jiang L 

PROVIDER: S-EPMC12775823 | biostudies-literature | 2026

REPOSITORIES: biostudies-literature