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Amyloid beta deregulates astroglial mGluR5-mediated calcium signaling via calcineurin and Nf-kB.
MedLine Citation:
PMID:  23616440     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
The amyloid hypothesis of Alzheimer's disease (AD) suggests that soluble amyloid β (Aβ) is an initiator of a cascade of events eventually leading to neurodegeneration. Recently, we reported that Aβ deranged Ca(2+) homeostasis specifically in hippocampal astrocytes by targeting key elements of Ca(2+) signaling, such as mGluR5 and IP3 R1. In the present study, we dissect a cascade of signaling events by which Aβ deregulates glial Ca(2+) : (i) 100 nM Aβ leads to an increase in cytosolic calcium after 4-6 h of treatment; (ii) mGluR5 is increased after 24 h of treatment; (iii) this increase is blocked by inhibitors of calcineurin (CaN) and NF-kB. Furthermore, we show that Aβ treatment of glial cells leads to de-phosphorylation of Bcl10 and an increased CaN-Bcl10 interaction. Last, mGluR5 staining is augmented in hippocampal astrocytes of AD patients in proximity of Aβ plaques and co-localizes with nuclear accumulation of the p65 NF-kB subunit and increased staining of CaNAα. Taken together our data suggest that nanomolar [Aβ] deregulates Ca(2+) homeostasis via CaN and its downstream target NF-kB, possibly via the cross-talk of Bcl10 in hippocampal astrocytes.
Authors:
Dmitry Lim; Anand Iyer; Virginia Ronco; Ambra A Grolla; Pier Luigi Canonico; Eleonora Aronica; Armando A Genazzani
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-4-25
Journal Detail:
Title:  Glia     Volume:  -     ISSN:  1098-1136     ISO Abbreviation:  Glia     Publication Date:  2013 Apr 
Date Detail:
Created Date:  2013-4-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8806785     Medline TA:  Glia     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2013 Wiley Periodicals, Inc., a Wiley company.
Affiliation:
Department of Pharmaceutical Sciences, Università degli Studi del Piemonte Orientale "Amedeo Avogadro,", Novara, Italy.
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