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Cell Calcium. 2014 Apr;55(4):219-29. doi: 10.1016/j.ceca.2014.02.016. Epub 2014 Mar 2.

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

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Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy.
Christian Doppler Laboratory for Flow Chemistry (CDLFC), Institute of Chemistry, Karl-Franzens-University Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
Faculty of Life Sciences, University of Manchester, Manchester M13 9PL, UK; IKERBASQUE, Basque Foundation for Science, 48011 Bilbao, Spain; Department of Neurosciences, University of the Basque Country UPV/EHU and CIBERNED, 48940 Leioa, Spain.
Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro", 28100 Novara, Italy. Electronic address:


In Alzheimer's disease (AD), astrocytes undergo complex morphological and functional changes that include early atrophy, reactive activation and Ca(2+) deregulation. Recently, we proposed a mechanism by which nanomolar Aβ42 deregulates mGluR5 and InsP3 receptors, the key elements of astrocytic Ca(2+) signalling toolkit. To evaluate the specificity of these changes, we have now investigated whether the effects of Aβ42 on Ca(2+) 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 Ca(2+) signals and store operated Ca(2+) entry (SOCE) were augmented in Aβ42-treated cells due to up-regulation of a set of Ca(2+) 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 Ca(2+) signalling differ from and may contrast to the effects of pro-inflammatory agents.


Alzheimer disease; Astrocytes; Ca(2+) signalling; Ca(2+) stores; Cytokines; Store-operated Ca(2+) entry; β-Amyloid

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