期刊
JOURNAL OF ALZHEIMERS DISEASE
卷 17, 期 1, 页码 59-68出版社
IOS PRESS
DOI: 10.3233/JAD-2009-1045
关键词
Alzheimer's disease; amyloid-beta; neocortical areas; RAGE; synaptic plasticity
资金
- Alzheimer's Disease Research, a program of American Health Assistance Foundation [A2008-335]
- NIH [P01AG17490]
- Italian Ministero Universita e Ricerca [PRIN, 2006]
- NATIONAL INSTITUTE ON AGING [P01AG017490] Funding Source: NIH RePORTER
Oligomeric amyloid-beta (A beta) interferes with long term potentiation (LTP) and cognitive processes, suggesting that A beta peptides may play a role in the neuronal dysfunction which characterizes the early stages of Alzheimer's disease (AD). Multiple lines of evidence have highlighted RAGE (receptor for advanced glycation end-products) as a receptor involved in A beta-induced neuronal and synaptic dysfunction. In the present study, we investigated the effect of oligomeric soluble A beta(1-42) on LTP elicited by the stimulation of different intracortical pathways in the mouse visual cortex. A variety of nanomolar concentrations (20-200 nM) of A beta(1-42) were able to inhibit LTP in cortical layer II-III induced by either white matter (WM-Layer II/III) or the layer II/III (horizontal pathway) stimulation, whereas the inhibition of LTP was more susceptible to A beta(1-42), which occurred at 20 nM of A beta, when stimulating layer II-III horizontal pathway. Remarkably, cortical slices were resistant to nanomolar A beta(1-42) in the absence of RAGE (genetic deletion of RAGE) or blocking RAGE by RAGE antibody. These results indicate that nanomolar A beta inhibits LTP expression in different neocortical circuits. Crucially, it is demonstrated that A beta-induced reduction of LTP in different cortical pathways is mediated by RAGE.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据