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Aβ-Dependent Inhibition of LTP in Different Intracortical Circuits of the Visual Cortex: The Role of RAGE
Origlia, Nicola Capsoni, Simona Cattaneo, Antonino Fang, Fang Arancio, Ottavio Yan, Shirley ShiDu Domenici, Luciano
Origlia, Nicola
Capsoni, Simona
Cattaneo, Antonino
Fang, Fang
Arancio, Ottavio
Yan, Shirley ShiDu
Domenici, Luciano
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Abstract
Oligomeric amyloid-β (Aβ) interferes with long term potentiation (LTP) and cognitive processes, suggesting that Aβ 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 Aβ-induced neuronal and synaptic dysfunction. In the present study, we investigated the effect of oligomeric soluble Aβ_{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 Aβ_{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 Aβ_{1-42}, which occurred at 20 nM of Aβ, when stimulating layer II-III horizontal pathway. Remarkably, cortical slices were resistant to nanomolar Aβ_{1-42} in the absence of RAGE (genetic deletion of RAGE) or blocking RAGE by RAGE antibody. These results indicate that nanomolar Aβ inhibits LTP expression in different neocortical circuits. Crucially, it is demonstrated that Aβ-induced reduction of LTP in different cortical pathways is mediated by RAGE.
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This is the publisher's version, also available electronically from http://iospress.metapress.com/content/u12738257q258710/?issue=1&genre=article&spage=59&issn=1387-2877&volume=17
Date
2009-05
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IOS Press
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Keywords
Alzheimer's disease, amyloid-β, Neocortical areas, RAGE, Synaptic plasticity
Citation
Origlia, Nicola et al. (2009). Aβ-Dependent Inhibition of LTP in Different Intracortical Circuits of the Visual Cortex: The Role of RAGE. Journal of Alzheimer's Disease 17(1):59-68. http://www.dx.doi.org/10.3233/JAD-2009-1045