Novel histone deacetylase-5 inhibitor T2943 exerts an anti-depressive effect in mice by enhancing GRID1 expression.

ABSTRACT: Histone deacetylase-5 (HDAC5) is implicated in the pathogenesis of depression and the mechanistic pathways underlying the effects of antidepressant medications. We previously identified a novel HDAC5 inhibitor, T2943, with antidepressant properties that promote histone 3 lysine-14 acetylation (H3K14ac) by inhibiting HDAC5 activity. In this study, we identify the core genes promoting transcription and expression following T2943-mediated upregulation of H3K14ac, highlighting Grid1 (GluD1) as a central gene. We used cleavage under targets and tagmentation (CUT&Tag), gene set enrichment analysis, and behavioral tests after GRID1 (glutamate receptor delta-1 subunit) knockdown. Gene ontology and pathway enrichment analysis via CUT&Tag suggested the following mechanism for the antidepressant acti

SUBMITTER: Du J 

PROVIDER: S-EPMC11802911 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature