Differential deregulation of astrocytic calcium signalling by amyloid-β, TNFα, IL-1β and LPS

Virginia Ronco, Ambra A. Grolla, Toma N. Glasnov, Pier Luigi Canonico, Alexei Verkhratsky, Armando A. Genazzani, Dmitry Lim

    Research output: Contribution to journalArticlepeer-review


    In Alzheimer's disease (AD), astrocytes undergo complex morphological and functional changes that include early atrophy, reactive activation and Ca2+ deregulation. Recently, we proposed a mechanism by which nanomolar Aβ42 deregulates mGluR5 and InsP3 receptors, the key elements of astrocytic Ca2+ signalling toolkit. To evaluate the specificity of these changes, we have now investigated whether the effects of Aβ42 on Ca2+ signalling machinery can be reproduced by pro-inflammatory agents (TNFα, IL-1β, LPS). Here we report that Aβ42 (100nM, 72h) significantly increased mRNA levels of mGluR5, InsP3R1 and InsP3R2, whereas pro-inflammatory agents reduced expression of these specific mRNAs. Furthermore, DHPG-induced Ca2+ signals and store operated Ca2+ entry (SOCE) were augmented in Aβ42-treated cells due to up-regulation of a set of Ca2+ signalling-related genes including TRPC1 and TRPC4. Opposite changes were observed when astrocytes were treated with TNFα, IL-1β and LPS. Last, the effects observed on SOCE by treating wild-type astrocytes with Aβ42 were also identified in untreated astrocytes from 3×Tg-AD animals, suggesting a link to the AD pathology. Our results demonstrate that effects of Aβ42 on astrocytic Ca2+ signalling differ from and may contrast to the effects of pro-inflammatory agents. © 2014 Elsevier Ltd.
    Original languageEnglish
    Pages (from-to)219-229
    Number of pages10
    JournalCell calcium
    Issue number4
    Publication statusPublished - 2014


    • Alzheimer disease
    • Astrocytes
    • Cytokines
    • β-Amyloid


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