Abstract
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 language | English |
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Pages (from-to) | 219-229 |
Number of pages | 10 |
Journal | Cell calcium |
Volume | 55 |
Issue number | 4 |
DOIs | |
Publication status | Published - 2014 |
Keywords
- Alzheimer disease
- Astrocytes
- Cytokines
- β-Amyloid