CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture

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http://hdl.handle.net/10138/166679

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Forsberg , D , Horn , Z , Tserga , E , Smedler , E , Silberberg , G , Shvarev , Y , Kaila , K , Uhlen , P & Herlenius , E 2016 , ' CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture ' , eLife , vol. 5 , 14170 . https://doi.org/10.7554/elife.14170

Title: CO2-evoked release of PGE2 modulates sighs and inspiration as demonstrated in brainstem organotypic culture
Author: Forsberg, David; Horn, Zachi; Tserga, Evangelia; Smedler, Erik; Silberberg, Gilad; Shvarev, Yuri; Kaila, Kai; Uhlen, Per; Herlenius, Eric
Contributor: University of Helsinki, Biosciences
Date: 2016-07-05
Language: eng
Number of pages: 41
Belongs to series: eLife
ISSN: 2050-084X
URI: http://hdl.handle.net/10138/166679
Abstract: Inflammation-induced release of prostaglandin E-2 (PGE(2)) changes breathing patterns and the response to CO2 levels. This may have fatal consequences in newborn babies and result in sudden infant death. To elucidate the underlying mechanisms, we present a novel breathing brainstem organotypic culture that generates rhythmic neural network and motor activity for 3 weeks. We show that increased CO2 elicits a gap junction-dependent release of PGE(2). This alters neural network activity in the preBotzinger rhythm-generating complex and in the chemosensitive brainstem respiratory regions, thereby increasing sigh frequency and the depth of inspiration. We used mice lacking eicosanoid prostanoid 3 receptors (EP3R), breathing brainstem organotypic slices and optogenetic inhibition of EP3R(+/+) cells to demonstrate that the EP3R is important for the ventilatory response to hypercapnia. Our study identifies a novel pathway linking the inflammatory and respiratory systems, with implications for inspiration and sighs throughout life, and the ability to autoresuscitate when breathing fails.
Subject: PRE-BOTZINGER COMPLEX
HIPPOCAMPAL SLICE CULTURES
PREBOTZINGER COMPLEX
GAP-JUNCTIONS
RESPIRATORY CHEMOSENSITIVITY
RETROTRAPEZOID NUCLEUS
SEROTONERGIC NEURONS
PRETERM INFANTS
SPINAL-CORD
NETWORKS
3112 Neurosciences
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