Hypoxia-induced loss of synaptic transmission is exacerbated in hippocampal slices of transgenic mice expressing C-terminal fragments of Alzheimer amyloid precursor protein

To investigate the possible involvement of beta-amyloid (AP) in disrupting neuronal function during ischemia, we examined whether overexpression of C- terminal fragments of beta-amyloid precursor protein (beta-APP) in transgen ic (Tg) mice is capable of altering the capacity of hippocampus slices to r ecover synaptic transmission after transient hypoxic episodes. Recovery of synaptic transmission was monitored in area CA(1) of perfused hippocampal s lices prepared from both control and Tg mice. The results obtained indicate that hippocampal slices prepared from Tg mice exhibited a much lower level of recovery in synaptic transmission following reoxygenation. This reducti on in the capacity of Tg slices to recover from hypoxia-induced impairment of synaptic transmission in the hippocampus does not appear to be related t o pre-existing alterations in either functional or biochemical properties o f glutamate receptors in Tg mice. The present results provide the first exp erimental evidence that overexpression of the C-terminal fragment of APP ex acerbates functional damage of hippocampal neurons after hypoxic episodes. (C) 1999 Wiley-Liss, Inc.