Putative roles of glutamate and glutathione in beta-amyloid-mediated hippocampal synaptic plasticity disruption in vivo

Abstract

The mechanisms underlying beta-amyloid (Aβ) protein-meditated disruption of synaptic plasticity in the CA1 region of the rat hippocampus in vivo were investigated using water soluble Aβ, both in synthetic preparations and in extracts of Alzheimer’s disease brain, that are known to inhibit long term potentiation (LTP) in urethane anaesthetized rats. Here we compared the ability of different aggregation states of synthetic wild-type Aβ-40 and dityrosine cross-linked Api-40 dimers, (Aβ-40)DiY, to inhibit LTP. We found the aggregated forms, but not their precursors, inhibit LTP in rats. This synaptic plasticity disruption was similar to that caused by pre aggregated preparations of water soluble Aβ-42 derived diffusible ligands (ADDL) or covalently cross-linked Aβ-40S26C dimers. Considering the significant role of glutamate receptors in Aβ pathology, we investigated the impact of modifying glutamate homeostasis.