Portal de Periódicos da CAPES

Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer’s disease transgenic mice

2022; eLife Sciences Publications Ltd; Volume: 11; Linguagem: Inglês

10.7554/elife.75055

2050-084X

Knut Sindre Åbjørsbråten, Gry HE Syverstad Skaaraas, Céline Cunen, Daniel M. Bjørnstad, Kristin M. Gullestad Binder, Laura Bojarskaite, Vidar R. Jensen, Lars Nilsson, Shreyas Balachandra Rao, Wannan Tang, Gudmund Horn Hermansen, Erlend A. Nagelhus, Ole Petter Ottersen, Reidun Torp, Rune Enger,

Neuroinflammation and Neurodegeneration Mechanisms

Increased astrocytic Ca 2+ signaling has been shown in Alzheimer’s disease mouse models, but to date no reports have characterized behaviorally induced astrocytic Ca 2+ signaling in such mice. Here, we employ an event-based algorithm to assess astrocytic Ca 2+ 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 Ca 2+ response to locomotion and an uncoupling of pupil responses and astrocytic Ca 2+ signaling in 15-month-old plaque-bearing mice. Using the genetically encoded fluorescent norepinephrine sensor GRAB NE , 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 Ca 2+ responses. Our data points to a dysfunction in the norepinephrine–astrocyte Ca 2+ activity axis, which may account for some of the cognitive deficits observed in Alzheimer’s disease.