Astrocytes release prostaglandin E2 to modify respiratory network activity
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.
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Author details
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.
Reviewing Editor
- Jan-Marino Ramirez, Seattle Children's Research Institute and University of Washington, United States
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).
Version history
- Received: June 19, 2017
- Accepted: October 3, 2017
- Accepted Manuscript published: October 4, 2017 (version 1)
- 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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