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.

Abeta-dependent Inhibition of LTP in different intracortical circuits of the visual cortex: the role of RAGE

CAPSONI, Simona;
2009

Abstract

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.
2009
Origlia, N; Capsoni, Simona; Cattaneo, A; Fang, F; Arancio, O; Yan, Sd; Domenici, L.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11392/2349946
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