Astrocytes release prostaglandin E2 to modify respiratory network activity

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...

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Main Authors: David Forsberg, Thomas Ringstedt, Eric Herlenius
Format: Article
Language:English
Published: eLife Sciences Publications Ltd 2017-10-01
Series:eLife
Subjects:
Online Access:https://elifesciences.org/articles/29566
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author David Forsberg
Thomas Ringstedt
Eric Herlenius
author_facet David Forsberg
Thomas Ringstedt
Eric Herlenius
author_sort David Forsberg
collection DOAJ
description 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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spelling doaj.art-11cdd557dda5419f8d4bda33432e88212022-12-22T04:32:18ZengeLife Sciences Publications LtdeLife2050-084X2017-10-01610.7554/eLife.29566Astrocytes release prostaglandin E2 to modify respiratory network activityDavid Forsberg0https://orcid.org/0000-0002-4719-2201Thomas Ringstedt1https://orcid.org/0000-0003-0294-9351Eric Herlenius2https://orcid.org/0000-0002-6859-0620Department of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenDepartment of Women’s and Children’s Health, Karolinska Institutet, Karolinska University Hospital, Stockholm, SwedenPreviously (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.https://elifesciences.org/articles/29566astrocytesbrainstemrespirationprostaglandinsneural networkchemosensitivity
spellingShingle David Forsberg
Thomas Ringstedt
Eric Herlenius
Astrocytes release prostaglandin E2 to modify respiratory network activity
eLife
astrocytes
brainstem
respiration
prostaglandins
neural network
chemosensitivity
title Astrocytes release prostaglandin E2 to modify respiratory network activity
title_full Astrocytes release prostaglandin E2 to modify respiratory network activity
title_fullStr Astrocytes release prostaglandin E2 to modify respiratory network activity
title_full_unstemmed Astrocytes release prostaglandin E2 to modify respiratory network activity
title_short Astrocytes release prostaglandin E2 to modify respiratory network activity
title_sort astrocytes release prostaglandin e2 to modify respiratory network activity
topic astrocytes
brainstem
respiration
prostaglandins
neural network
chemosensitivity
url https://elifesciences.org/articles/29566
work_keys_str_mv AT davidforsberg astrocytesreleaseprostaglandine2tomodifyrespiratorynetworkactivity
AT thomasringstedt astrocytesreleaseprostaglandine2tomodifyrespiratorynetworkactivity
AT ericherlenius astrocytesreleaseprostaglandine2tomodifyrespiratorynetworkactivity