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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Format: | Article |
Language: | English |
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eLife Sciences Publications Ltd
2017-10-01
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Series: | eLife |
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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. |
first_indexed | 2024-04-11T09:16:44Z |
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institution | Directory Open Access Journal |
issn | 2050-084X |
language | English |
last_indexed | 2024-04-11T09:16:44Z |
publishDate | 2017-10-01 |
publisher | eLife Sciences Publications Ltd |
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series | eLife |
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 |