Accumulation of GSK-3β in Interneurons Impairs Adult Hippocampal Neurogenesis by Inhibiting GABAergic Transmission.

ABSTRACT: The activation of glycogen synthase kinase 3β (GSK-3β) and the deterioration of spatial memory represent prominent pathological and clinical manifestations of Alzheimer's disease (AD). Nevertheless, the precise intrinsic mechanisms linking these pathological features remain poorly elucidated. In this study, we identified significant upregulation of GSK-3β activity in inhibitory interneurons within the hippocampal dentate gyrus (DG) of 3×Tg-AD mice. Subsequent investigations demonstrated that targeted overexpression of GSK-3β in these interneurons triggered aberrant activation of neural stem cells (NSCs), culminating in apoptotic cell death and consequent deficits in adult hippocampal neurogenesis (AHN). Utilizing in vivo fiber-optic recording techniques, we further established that GSK-3β

SUBMITTER: Liu F 

PROVIDER: S-EPMC12341769 | biostudies-literature | 2025 Aug

REPOSITORIES: biostudies-literature