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  • Title: Amyloid-β and Alzheimer's disease type pathology differentially affects the calcium signalling toolkit in astrocytes from different brain regions.
    Author: Grolla AA, Sim JA, Lim D, Rodriguez JJ, Genazzani AA, Verkhratsky A.
    Journal: Cell Death Dis; 2013 May 09; 4(5):e623. PubMed ID: 23661001.
    Abstract:
    The entorhinal-hippocampal circuit is severely affected in Alzheimer's disease (AD). Here, we demonstrate that amyloid-β (Aβ) differentially affects primary cultured astrocytes derived from the entorhinal cortex (EC) and from the hippocampus from non-transgenic controls and 3xTg-AD transgenic mice. Exposure to 100 nM of Aβ resulted in increased expression of the metabotropic glutamate receptor type 5 (mGluR5) and its downstream InsP3 receptor type 1 (InsP3R1) in hippocampal but not in EC astrocytes. Amplitudes of Ca(2+) responses to an mGluR5 agonist, DHPG, and to ATP, another metabotropic agonist coupled to InsP3Rs, were significantly increased in Aβ-treated hippocampal but not in EC astrocytes. Previously we demonstrated that senile plaque formation in 3xTg-AD mice triggers astrogliosis in hippocampal but not in EC astrocytes. The different sensitivities of the Ca(2+) signalling toolkit of EC versus hippocampal astrocytes to Aβ may account for the lack of astrogliosis in the EC, which in turn can explain the higher vulnerability of this region to AD.
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