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 β-amyloid (Aβ) in disrupting neuronal function during ischemia, we examined whether overexpression of C-terminal fragments of β-amyloid precursor protein (β-APP) in transgenic (Tg) mice is capable of altering the capacity of hippocampus slices to recover synaptic transmission after transient hypoxic episodes. Recovery of synaptic transmission was monitored in area CA₁ of perfused hippocampal slices 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 reduction in the capacity of Tg slices to recover from hypoxia-induced impairment of synaptic transmission in the hippocampus does not appear to be related to pre-existing alterations in either functional or biochemical properties of glutamate receptors in Tg mice. The present results provide the first experimental evidence that overexpression of the C-terminal fragment of APP exacerbates functional damage of hippocampal neurons after hypoxic episodes.