期刊
NEUROBIOLOGY OF AGING
卷 33, 期 7, 页码 -出版社
ELSEVIER SCIENCE INC
DOI: 10.1016/j.neurobiolaging.2011.12.010
关键词
LTP; Perforant path; Plaque histology; Electrophysiology; Nucleus pontis oralis; APP; PS1; EEG; Alzheimer's disease; Biomarker
资金
- Pfizer Global Research and Development, Groton, CT, USA
Transgenic mice are used to model increased brain amyloid-beta (A beta) and amyloid plaque formation reflecting Alzheimer's disease pathology. In our study hippocampal network oscillations, population spikes, and long-term potentiation (LTP) were recorded in APPswe/PS1dE9 (APP/PS1) and presenilin1 (PS1) transgenic and wild type mice at 2, 4, and 8 months of age under urethane anesthesia. Hippocampal theta oscillations elicited by brainstem stimulation were similar in wild type and PS1 mice at all age groups. In contrast, APP/PS1 mice showed an age-dependent decrease in hippocampal activity, characterized by a significant decline in elicited theta power and frequency at 4 and 8 months. Magnitudes of population spikes and long-term potentiation in the dentate gyrus were similar across groups at both 4 and 8 months. In APP/PS1 mice, soluble and insoluble A beta, and hippocampal and cortical plaque load increased with age, and the disruption in hippocampal theta oscillation showed a significant correlation with plaque load. Our study shows that, using in vivo electrophysiological methods, early A beta-related functional deficits can be robustly detected in the brainstem-hippocampus multisynaptic network. (C) 2012 Elsevier Inc. All rights reserved.
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