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    RAGE Inhibition in Microglia Prevents Ischemia-Dependent Synaptic Dysfunction in an Amyloid-Enriched Environment

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    Origlia_RAGE2014.pdf (3.878Mb)
    Issue Date
    2014-06-25
    Author
    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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    Abstract
    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.
    Description
    This is the published version. Copyright 2014 Origlia et. al.
    URI
    http://hdl.handle.net/1808/19140
    DOI
    https://doi.org/10.1523/JNEUROSCI.0141-14.2014
    Collections
    • Pharmaceutical Chemistry Scholarly Works [288]
    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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    KU Libraries
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    Lawrence, KS 66045
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    Contact KU ScholarWorks
    785-864-8983
    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    785-864-8983

    KU Libraries
    1425 Jayhawk Blvd
    Lawrence, KS 66045
    Image Credits
     

     

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