Impaired astrocytic Ca 2+ signaling in awake-behaving Alzheimer's disease transgenic mice.

Autor:	Åbjørsbråten KS; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Skaaraas GHES; Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Cunen C; Statistics and Data Science group, Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway.; Norwegian Computing Center, Oslo, Norway., Bjørnstad DM; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Binder KMG; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Bojarskaite L; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.; Department of Neurology, Oslo University Hospital, Oslo, Norway., Jensen V; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Nilsson LNG; Department of Pharmacology, University of Oslo and Oslo University Hospital, Oslo, Norway., Rao SB; Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Tang W; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway., Hermansen GH; Statistics and Data Science group, Department of Mathematics, Faculty of Mathematics and Natural Sciences, University of Oslo, Oslo, Norway., Nagelhus EA; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Ottersen OP; Office of the President, Karolinska Institutet, Stockholm, Sweden., Torp R; Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway., Enger R; GliaLab at the Letten Centre, Division of Anatomy, Department of Molecular Medicine, Institute of Basic Medical Sciences, University of Oslo, Oslo, Norway.
Jazyk:	angličtina
Zdroj:	ELife [Elife] 2022 Jul 14; Vol. 11. Date of Electronic Publication: 2022 Jul 14.
DOI:	10.7554/eLife.75055
Abstrakt:	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. Competing Interests: KÅ, GS, CC, DB, KB, LB, VJ, LN, SR, WT, GH, EN, OO, RT, RE No competing interests declared (© 2022, Åbjørsbråten, Skaaraas et al.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu