Amyloid-β and Alzheimer's disease type pathology differentially affects the calcium signalling toolkit in astrocytes from different brain regions

The entorhinal-hippocampal circuit is severely affected in Alzheimer's disease (AD). Here, we demonstrate that amyloid-beta (A beta) 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 A beta resulted in increased expression of the metabotropic glutamate receptor type 5 (mGluR5) and its downstream InsP(3) receptor type 1 (InsP(3)R1) in hippocampal but not in EC astrocytes. Amplitudes of Ca2+ responses to an mGluR5 agonist, DHPG, and to ATP, another metabotropic agonist coupled to InsP(3)Rs, were significantly increased in Ab beta-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 Ca2+ signalling toolkit of EC versus hippocampal astrocytes to A beta may account for the lack of astrogliosis in the EC, which in turn can explain the higher vulnerability of this region to AD.