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Astrocytes release prostaglandin E2 to modify respiratory network activity

  1. David Forsberg  Is a corresponding author
  2. Thomas Ringstedt
  3. Eric Herlenius
  1. Karolinska Institutet, Sweden
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Cite this article as: eLife 2017;6:e29566 doi: 10.7554/eLife.29566

Abstract

Previously (Forsberg et al., 2016), we revealed that prostaglandin E2 (PGE2), released during hypercapnic challenge, increases calcium oscillations in the chemosensitive parafacial respiratory group (pFRG/RTN). Here, we demonstrate that pFRG/RTN astrocytes are the PGE2 source. Two distinct astrocyte subtypes were found using transgenic mice expressing GFP and MrgA1 receptors in astrocytes. Although most astrocytes appeared dormant during time-lapse calcium imaging, a subgroup displayed persistent, rhythmic oscillating calcium activity. These active astrocytes formed a subnetwork within the respiratory network distinct from the neuronal network. Activation of exogenous MrgA1Rs expressed in astrocytes tripled astrocytic calcium oscillation frequency in both the preBötzinger complex and pFRG/RTN. However, neurons in the preBötC were unaffected, whereas neuronal calcium oscillatory frequency in pFRG/RTN doubled. Notably, astrocyte activation in pFRG/RTN triggered local PGE2 release and blunted the hypercapnic response. Thus, astrocytes play an active role in respiratory rhythm modulation, modifying respiratory-related behavior through PGE2 release in the pFRG/RTN.

Article and author information

Author details

  1. David Forsberg

    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
    For correspondence
    david.forsberg@ki.se
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-4719-2201
  2. Thomas Ringstedt

    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  3. Eric Herlenius

    Department of Women's and Children's Health, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    Eric Herlenius, employed at the Karolinska Institutet and the Karolinska University Hospital and is a coinventor of a patent application regarding biomarkers and their relation to breathing disorders, WO2009063226..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-6859-0620

Funding

Karolinska Institutet

  • David Forsberg
  • Eric Herlenius

Swedish Research Council (EH 2016-01111)

  • Eric Herlenius

Hjärnfonden (EH FO2017-0203)

  • Eric Herlenius

M & M Wallenberg Foundation (EH 102179)

  • Eric Herlenius

Stockholms Läns Landsting (EH 20140011)

  • Eric Herlenius

Freemasons Children's House

  • David Forsberg
  • Eric Herlenius

Swedish National Heart and Lung Foundation (20150558)

  • Eric Herlenius

Swedish National Heart and Lung Foundation (20160549)

  • David Forsberg

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 studies were performed in strict accordance with European Community Guidelines and protocols approved by the regional ethic committee (Permit numbers: N247/13 and N265/14b).

Reviewing Editor

  1. Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States

Publication history

  1. Received: June 19, 2017
  2. Accepted: October 3, 2017
  3. Accepted Manuscript published: October 4, 2017 (version 1)
  4. Version of Record published: October 19, 2017 (version 2)

Copyright

© 2017, Forsberg 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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