Early hippocampal synaptic plasticity and episodic like-memory deficits in a transgenic mouse model of Alzheimer disease - involvment of corticosterone

Ingrid Bethus,Elisabeth Raymond,Helene Marie,Fabien Lanté,Magda Chafai,Ana Salgueiro Peirera

doi:10.1186/1750-1326-8-s1-p62

Abstract

Background The etiology of Alzheimer’s disease (AD) is unclear and no cure is yet available. The function of the hippocampus, a key structure responsible for memory encoding and consolidation, is affected early in AD leading to progressive irreversible memory loss. There is strong evidence that AD onset is, at least partly, due to accumulation within the hippocampus of peptides processed from the amyloid precursor protein APP, such as amyloid-beta (A?). Also, several studies demonstrated an abnormal elevation in the main stress hormone, cortisol (CORT in mice), in the initial phase of AD in patients and in mouse models. Here, we investigated if early co-accumulation of CORT and APP-derived peptides could be a main trigger driving the onset of memory deficits in AD.

Highlights

The etiology of Alzheimer’s disease (AD) is unclear and no cure is yet available
We investigated if early co-accumulation of CORT and APP-derived peptides could be a main trigger driving the onset of memory deficits in AD
We show that at 4 months of age, an age where A? begins to accumulate, Tg2576 mice already display enhanced NMDA receptor-dependent long term depression (LTD), but unchanged long term potentiation (LTP), in CA1 pyramidal neurons compared to WT littermates

Summary

Introduction

The etiology of Alzheimer’s disease (AD) is unclear and no cure is yet available. The function of the hippocampus, a key structure responsible for memory encoding and consolidation, is affected early in AD leading to progressive irreversible memory loss. There is strong evidence that AD onset is, at least partly, due to accumulation within the hippocampus of peptides processed from the amyloid precursor protein APP, such as amyloid-beta (A?). Several studies demonstrated an abnormal elevation in the main stress hormone, cortisol (CORT in mice), in the initial phase of AD in patients and in mouse models.

Methods

Results

Conclusion