RAGE Inhibition in Microglia Prevents Ischemia-Dependent Synaptic Dysfunction in an Amyloid-Enriched Environment
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Issue Date
2014-06-25Author
Origlia, Nicola
Criscuolo, Chiara
Arancio, Ottavio
Yan, Shirley ShiDu
Domenici, Luciano
Publisher
Society for Neuroscience
Type
Article
Article Version
Scholarly/refereed, publisher version
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Show full item recordAbstract
Ischemia is known to increase the deleterious effect of β-amyloid (Aβ), contributing to early cognitive impairment in Alzheimer's disease. Here, we investigated whether transient ischemia may function as a trigger for Aβ-dependent synaptic impairment in the entorhinal cortex (EC), acting through specific cellular signaling. We found that synaptic depression induced by oxygen glucose deprivation (OGD) was enhanced in EC slices either in presence of synthetic oligomeric Aβ or in slices from mutant human amyloid precursor protein transgenic mice (mhAPP J20). OGD-induced synaptic depression was ameliorated by functional suppression of RAGE. In particular, overexpression of the dominant-negative form of RAGE targeted to microglia (DNMSR) protects against OGD-induced synaptic impairment in an amyloid-enriched environment, reducing the activation of stress-related kinases (p38MAPK and JNK) and the release of IL-1β. Our results demonstrate a prominent role for the RAGE-dependent neuroinflammatory pathway in the synaptic failure induced by Aβ and triggered by transient ischemia.
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This is the published version. Copyright 2014 Origlia et. al.
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Citation
Origlia, N., C. Criscuolo, O. Arancio, S. S. Yan, and L. Domenici. "RAGE Inhibition in Microglia Prevents Ischemia-Dependent Synaptic Dysfunction in an Amyloid-Enriched Environment." Journal of Neuroscience 34.26 (2014): 8749-760. http://dx.doi.org/10.1523/JNEUROSCI.0141-14.2014
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