Spatiotemporal differential regulation of extrasynaptic GluN2B receptor subunits and PSA-NCAM in brain aging and Alzheimer's disease.

ABSTRACT:

Introduction

Extrasynaptic GluN2B N-methyl-D-aspartate receptors (ES-GluN2B) are localized outside synapses and promote excitotoxic signaling, apoptosis, and long-term depression (LTD) in Alzheimer's disease (AD). Polysialylated neural cell adhesion molecule (PSA-NCAM) physiologically inhibits ES-GluN2B activity, and its downregulation is associated with impaired synaptic plasticity. However, the spatiotemporal changes of ES-GluN2B and PSA-NCAM during brain aging versus AD remain poorly understood.

Methods

We investigated GluN2A, GluN2B, ES-GluN2B, and PSA-NCAM expression across brain regions in young and old Tg2576 AD and wild-type (WT) mice. Additional experiments included PSD-95 pulldown assays, analysis of GluN2B phosphorylation at Ser1480, CRISPRa-driven ST8Sia4 upregul

SUBMITTER: Imiruaye OE 

PROVIDER: S-EPMC12426952 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature