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Microglial Receptor for Advanced Glycation End Product-Dependent Signal Pathway Drives β-Amyloid-Induced Synaptic Depression and Long-Term Depression Impairment in Entorhinal Cortex

Origlia, Nicola
; 
Bonadonna, Camilla
; 
Rosellini, Alfredo
; 
Leznik, Elena
; 
Arancio, Ottavio
; 
Yan, Shirley ShiDu
; 
Domenici, Luciano
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Abstract
Overproduction of β-amyloid (Aβ) is a pathologic feature of Alzheimer's disease, leading to cognitive impairment. Here, we investigated the impact of cell-specific receptor for advanced glycation end products (RAGE) on Aβ-induced entorhinal cortex (EC) synaptic dysfunction. We found both a transient depression of basal synaptic transmission and inhibition of long-term depression (LTD) after the application of Aβ in EC slices. Synaptic depression and LTD impairment induced by Aβ were rescued by functional suppression of RAGE. Remarkably, the rescue was only observed in slices from mice expressing a defective form of RAGE targeted to microglia, but not in slices from mice expressing defective RAGE targeted to neurons. Moreover, we found that the inflammatory cytokine IL-1β (interleukin-1β) and stress-activated kinases [p38 MAPK (p38 mitogen-activated protein kinase) and JNK (c-Jun N-terminal kinase)] were significantly altered and involved in RAGE signaling pathways depending on RAGE expression in neuron or microglia. These findings suggest a prominent role of microglial RAGE signaling in Aβ-induced EC synaptic dysfunction.
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This is the publisher's version, also available electronically from http://www.jneurosci.org/content/30/34/11414
Date
2010-08-25
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Sociey for Neuroscience
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Pharmacy Scholarly Works
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Origlia, Nicola et al. (2010). Microglial Receptor for Advanced Glycation End Product-Dependent Signal Pathway Drives β-Amyloid-Induced Synaptic Depression and Long-Term Depression Impairment in Entorhinal Cortex. Journal of Neuroscience 30(34):11414-11425. http://www.dx.doi.org/10.1523/JNEUROSCI.2127-10.2010
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https://hdl.handle.net/1808/14811
DOI
10.1523/JNEUROSCI.2127-10.2010
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