Early changes in A beta levels in the brain of APPswe transgenic mice - Implication on synaptic density, alpha 7 neuronal nicotinic acetylcholine- and N-methyl-D-aspartate receptor levels

摘要

Tg 2576 (APPswe) mice develop age-related amyloid deposition as well as behavioural- and electrophysiological changes in the brain. In this study, APPswe mice were investigated from 7 to 90 days of age. We observed high A 3 levels in the cortex of APPswe mice at 7 days of age, suggesting that these mice produce A beta from birth. A positive correlation between A 3 and synaptophysin levels, followed by changes in ERK MAPK activity, indicated that A beta causes altered synaptic function and an increase in the number of synaptic terminals. In addition, alterations in [I-125]alpha bungarotoxin- and [H-3]MK-801 binding sites were also observed in APPswe mice compared to controls. In conclusion, over-expression of A beta early in life causes changes in synaptophysin levels and number of [I-125]alpha bungarotoxin- and [H-3]MK-801 binding sites. The results may provide important information about the onset and consequences of A beta pathology in this transgenic mouse model. (c) 2005 Elsevier Inc. All rights reserved.