Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice
Åbjørsbråten, Knut Sindre; Skaaraas, Gry HE Syverstad; Cunen, Celine Marie Løken; Bjørnstad, Daniel Marelius; Binder, Kristin M Gullestad; Bojarskaite, Laura; Jensen, Vidar; Nilsson, Lars; Rao, Shreyas B.; Tang, Wannan; Hermansen, Gudmund Horn; Nagelhus, Erlend Arnulf; Ottersen, Ole Petter; Torp, Reidun; Enger, Rune
Peer reviewed, Journal article
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Date
2022Metadata
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10.7554/eLife.75055Abstract
Increased astrocytic Ca2+ signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca2+ signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca2+ signals in the neocortex of awake-behaving tg-ArcSwe mice and non-transgenic wildtype littermates while monitoring pupil responses and behavior. We demonstrate an attenuated astrocytic Ca2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca2+ signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRABNE, we demonstrate a reduced norepinephrine signaling during spontaneous running and startle responses in the transgenic mice, providing a possible mechanistic underpinning of the observed reduced astrocytic Ca2+ responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca2+ activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease.