Hippocampal Zkscan4 confers resilience to chronic stress-induced depression-like behaviors.

ABSTRACT: Major depression is a prevalent and devastating psychiatric disorder. However, our understanding of the underlying molecular mechanisms is limited. Here, we found reduced expression of zinc finger protein with Krüppel-associated box and SCAN domains 4 (Zkscan4) in the hippocampi of patients with major depressive disorder and stress-susceptible mice. Zkscan4 disruption (Zkscan4^-/-) was sufficient to induce depression-like behaviors following subthreshold social stress. Zkscan4 regulated excitatory synaptic transmission mainly through direct interaction with the Htr2a promoter and the recruitment of glucocorticoid receptors for the transcriptional repression of 5-hydroxytryptamine receptor 2a (Htr2a). Reduced excitatory synaptic transmission in the hippocampus and st

SUBMITTER: Gao K 

PROVIDER: S-EPMC12101508 | biostudies-literature | 2025 May

REPOSITORIES: biostudies-literature