title: Amyloid-β and Alzheimer's disease type pathology differentially affects the calcium signalling toolkit in astrocytes from different brain regions.
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.
authors: Dipartimento di Scienze del Farmaco, Università degli Studi del Piemonte Orientale Amedeo Avogadro, Novara 28100, Italy.
authors: A A
authors: AA
authors: Grolla
authors: J A
authors: JA
authors: Sim
authors: D
authors: D
authors: Lim
authors: J J
authors: JJ
authors: Rodriguez
authors: A A
authors: AA
authors: Genazzani
authors: A
authors: A
authors: Verkhratsky
mesh_terms: D000544:Alzheimer Disease / Q000378:metabolism / Q000473:pathology; D016229:Amyloid beta-Peptides / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D020013:Calcium Signaling / Q000187:drug effects; D002478:Cells, Cultured; D004195:Disease Models, Animal; D018728:Entorhinal Cortex / Q000166:cytology / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology / Q000378:metabolism*; D053496:Inositol 1,4,5-Trisphosphate Receptors / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; C578936:Grm5 protein, mouse; D053496:Inositol 1,4,5-Trisphosphate Receptors; D064529:Receptor, Metabotropic Glutamate 5; D018094:Receptors, Metabotropic Glutamate; D002118:Calcium
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