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 (A beta) in disrupting neuronal function during ischemia, we examined whether overexpression of C-terminal fragments of beta-amyloid precursor protein (beta-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.
Département de Chimie-Biologie, Université du Québec, Canada.
O
O
Ghribi
L
L
Lapierre
M
M
Girard
M
M
Ohayon
J
J
Nalbantoglu
G
G
Massicotte
D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis* / Q000737:chemistry; D000818:Animals; D019706:Excitatory Postsynaptic Potentials; D006624:Hippocampus / Q000473:pathology / Q000503:physiopathology*; D002534:Hypoxia, Brain / Q000473:pathology / Q000503:physiopathology*; D066298:In Vitro Techniques; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000473:pathology / Q000502:physiology; D010446:Peptide Fragments / Q000096:biosynthesis*; D017470:Receptors, Glutamate / Q000378:metabolism; D009435:Synaptic Transmission / Q000502:physiology*
D016564:Amyloid beta-Protein Precursor; D010446:Peptide Fragments; D017470:Receptors, Glutamate