Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer's disease transgenic mice
- University of Oslo, Norway
- Norwegian University of Science and Technology, Norway
- Karolinska Institute, Sweden
Abstract
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-months 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.
Data availability
The numerical data for the statistical analyses in Figures 3-5 are available as Source Data File 1. The complete dataset is available at http://dx.doi.org/10.11582/2021.00100.
Article and author information
Author details
Funding
Norges Forskningsråd (Grant 249988)
- Rune Enger
Norges Forskningsråd (Grant 302326)
- Rune Enger
Letten Foundation (Research support)
- Rune Enger
Olav Thon Stiftelsen (Olav Thon Award)
- Erlend A Nagelhus
Helse Sør-Øst RHF (Grant 2016070)
- Rune Enger
Norges Forskningsråd (Medical Student Research Program)
- Kristin M Binder
Helse Sør-Øst RHF (2020039)
- Rune Enger
Norges Forskningsråd (Grant 271555/F20)
- Kristin M Binder
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Reviewing Editor
- Mark T Nelson, University of Vermont, United States
Ethics
Animal experimentation: The study was performed in strict accordance with the Guide for the Care and Use of Laboratory Animals of the National Institutes of Health and approved by the Norwegian Food Safety Authority (project number: FOTS #11983).
Version history
- Received: October 28, 2021
- Preprint posted: November 24, 2021 (view preprint)
- Accepted: June 29, 2022
- Accepted Manuscript published: July 14, 2022 (version 1)
- Version of Record published: August 4, 2022 (version 2)
Copyright
© 2022, Åbjørsbråten et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer's disease transgenic mice
eLife 11:e75055.
https://doi.org/10.7554/eLife.75055
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