Abeta-dependent Inhibition of LTP in different intracortical circuits of the visual cortex: the role of RAGE.
Oligomeric amyloid-beta (Abeta) interferes with long-term potentiation (LTP) and cognitive processes, suggesting that Abeta 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 Abeta-induced neuronal and synaptic dysfunction. In the present study, we investigated the effect of oligomeric soluble Abeta1-42 on LTP elicited by the stimulation of different intracortical pathways in the mouse visual cortex. A variety of nanomolar concentrations (20-200 nM) of Abeta1-42 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 Abeta1-42, which occurred at 20 nM of Abeta, when stimulating layer II-III horizontal pathway. Remarkably, cortical slices were resistant to nanomolar Abeta1-42 in the absence of RAGE (genetic deletion of RAGE) or blocking RAGE by RAGE antibody. These results indicate that nanomolar Abeta inhibits LTP expression in different neocortical circuits. Crucially, it is demonstrated that Abeta-induced reduction of LTP in different cortical pathways is mediated by RAGE.
Origlia
Nicola
N
Institute of Neuroscience (CNR), Pisa, Italy.
Capsoni
Simona
S
Cattaneo
Antonino
A
Fang
Fang
F
Arancio
Ottavio
O
Yan
Shi Du
SD
Domenici
Luciano
L
D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000906:Antibodies / Q000494:pharmacology; D001703:Biophysics; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation / Q000379:methods; D066298:In Vitro Techniques; D017774:Long-Term Potentiation / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020928:Mitogen-Activated Protein Kinases / Q000172:deficiency / Q000276:immunology / Q000378:metabolism*; D009415:Nerve Net / Q000502:physiology*; D009434:Neural Pathways / Q000502:physiology; D010446:Peptide Fragments / Q000494:pharmacology*; D014793:Visual Cortex / Q000187:drug effects / Q000502:physiology*
D016229:Amyloid beta-Peptides; D000906:Antibodies; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); C498977:Mok protein, mouse; D020928:Mitogen-Activated Protein Kinases