Inhibition of hippocampal mossy fiber plasticity and episodic memory by human Aβ oligomers is prevented by enhancing cAMP signaling in Alzheimer's mice.

ABSTRACT:

Introduction

Early episodic memory impairment in Alzheimer's disease (AD) is linked to synaptic dysfunction from amyloid β-protein oligomers (oAβ), particularly affecting the dentate gyrus mossy fiber-CA3 pathway. The APP^NL-G-F mouse model exhibits early deficits in mossy fiber long-term potentiation (mf-LTP).

Methods

We administered the β-adrenergic receptor agonist isoproterenol (ISO) in vivo and phosphodiesterase type 4 inhibitor GSK356278 in vitro to assess their impact on mf-LTP and contextual fear memory. Fluorescence lifetime imaging (FLIM)-Förster resonance energy transfer (FRET) microscopy was used to visualize impaired and rescued cyclic adenosine monophosphate (cAMP) signaling in dentate gyrus neurons.

Results

ISO prevented mf-LTP impairment at 3

SUBMITTER: Jin SX 

PROVIDER: S-EPMC12040739 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature