Enhanced synaptic potentiation in transgenic mice expressing presenilin 1 familial Alzheimer's disease mutation is normalized with a benzodiazepine

被引:54
作者
Zaman, SH
Parent, A
Laskey, A
Lee, MK
Borchelt, DR
Sisodia, SS
Malinow, R
机构
[1] Cold Spring Harbor Lab, Cold Spring Harbor, NY 11724 USA
[2] Johns Hopkins Univ, Sch Med, Neuropathol Lab, Baltimore, MD 21205 USA
[3] Univ Chicago, Dept Pharmacol, Chicago, IL 60637 USA
[4] Univ Chicago, Dept Physiol Sci, Chicago, IL 60637 USA
关键词
D O I
10.1006/nbdi.1999.0271
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Mutations in presenilin 1(PS1) are the most common causes of familial Alzheimer's disease (FAD). We examined synaptic physiology in hippocampal brain slices of transgenic mice expressing the FAD-linked PS1 deletion of exon 9 variant. Basal excitatory transmission and paired-pulse facilitation in PS1 mutant mice were unchanged. Short- and long-term potentiation of excitatory transmission following high-frequency stimulation were greater in transgenic mice expressing mutant PS1. Mutants had enhanced synaptic inhibition, which may be a compensatory change offsetting an abnormally sensitized plasticity of excitatory transmission. Increasing inhibitory transmission in mutant animals even more with a benzodiazepine reverted synaptic potentiation to the levels of controls. These results support the potential use of benzodiazepines in the treatment of familial Alzheimer's disease. (C) 2000 Academic Press.
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页码:54 / 63
页数:10
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