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.

The following data sets were generated

Article and author information

Author details

  1. Knut Sindre Åbjørsbråten

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  2. Gry HE Skaaraas

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  3. Céline Cunen

    Department of Mathematics, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  4. Daniel M Bjørnstad

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  5. Kristin M Binder

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  6. Laura Bojarskaite

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  7. Vidar Jensen

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  8. Lars NG Nilsson

    Department of Pharmacology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  9. Shreyas B Rao

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  10. Wannan Tang

    Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
    Competing interests
    The authors declare that no competing interests exist.
  11. Gudmund Horn Hermansen

    Department of Mathematics, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  12. Erlend A Nagelhus

    Department of Pharmacology, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  13. Ole Petter Ottersen

    Office of the President, Karolinska Institute, Stockholm, Sweden
    Competing interests
    The authors declare that no competing interests exist.
  14. Reidun Torp

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    Competing interests
    The authors declare that no competing interests exist.
  15. Rune Enger

    Department of Molecular Medicine, University of Oslo, Oslo, Norway
    For correspondence
    rune.enger@medisin.uio.no
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9418-7117

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.

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).

Reviewing Editor

  1. Mark T Nelson, University of Vermont, United States

Version history

  1. Received: October 28, 2021
  2. Preprint posted: November 24, 2021 (view preprint)
  3. Accepted: June 29, 2022
  4. Accepted Manuscript published: July 14, 2022 (version 1)
  5. 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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  1. Knut Sindre Åbjørsbråten
  2. Gry HE Skaaraas
  3. Céline Cunen
  4. Daniel M Bjørnstad
  5. Kristin M Binder
  6. Laura Bojarskaite
  7. Vidar Jensen
  8. Lars NG Nilsson
  9. Shreyas B Rao
  10. Wannan Tang
  11. Gudmund Horn Hermansen
  12. Erlend A Nagelhus
  13. Ole Petter Ottersen
  14. Reidun Torp
  15. Rune Enger
(2022)
Impaired astrocytic Ca2+ signaling in awake-behaving Alzheimer's disease transgenic mice
eLife 11:e75055.
https://doi.org/10.7554/eLife.75055

Share this article

https://doi.org/10.7554/eLife.75055

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