Host microbiota regulates central nervous system serotonin receptor 2C editing in rodents

Simple item page
dc.contributor.authorvan de Wouw, Marcel
dc.contributor.authorStilling, Roman M.
dc.contributor.authorPeterson, Veronica L.
dc.contributor.authorRyan, Feargal J.
dc.contributor.authorHoban, Alan E.
dc.contributor.authorShanahan, Fergus
dc.contributor.authorClarke, Gerard
dc.contributor.authorClaesson, Marcus J.
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.authorSchellekens, Harriët
dc.contributor.funderScience Foundation Irelanden
dc.contributor.funderMead Johnson Nutritionen
dc.contributor.funder4D Pharmaen
dc.contributor.funderSuntory Foundationen
dc.contributor.funderNutricia Research Foundationen
dc.date.accessioned2019-09-19T08:45:21Z
dc.date.available2019-09-19T08:45:21Z
dc.date.issued2019-08-15
dc.date.updated2019-09-19T08:29:46Z
dc.description.abstractMicrobial colonization of the gastrointestinal tract plays a crucial role in the development of enteric and central nervous system functionality. The serotonergic system has been heavily implicated in microbiota–gut–brain axis signaling, particularly in proof-of-principle studies in germ-free (GF) animals. One aspect of the serotonergic system that has been left unexplored in relation to the microbiota is the unique ability of the serotonin receptor 2C (5-HT2C) to undergo post-transcriptional editing, which has been implicated in decreased receptor functionality. We investigated whether GF mice, with absent microbiota from birth, have altered 5-HT2C receptor expression and editing in the brain, and if colonization of the microbiota is able to restore editing patterns. Next, we investigated whether microbiota depletion later in life using a chronic antibiotic treatment could affect 5-HT2C receptor editing patterns in rats. We found that GF mice have an increased prevalence of the edited 5-HT2C receptor isoforms in the amygdala, hypothalamus, prefrontal cortex, and striatum, which was partially normalized upon colonization post-weaning. However, no alterations were observed in the hypothalamus after microbiota depletion using an antibiotic treatment in adult rats. This suggests that alterations in the microbiome during development, but not later in life, could influence 5-HT2C receptor editing patterns. Overall, these results demonstrate that the microbiota affects 5-HT2C receptor editing in the brain and may inform novel therapeutic strategies in conditions in which 5-HT2C receptor editing is altered, such as depression.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationvan de Wouw, M., Stilling, R. M., Peterson, V. L., Ryan, F. J., Hoban, A. E., Shanahan, F., Clarke, G., Claesson, M. J., Dinan, T. G., Cryan, J. F. and Schellekens, H. (2019) 'Host Microbiota Regulates Central Nervous System Serotonin Receptor 2C Editing in Rodents', ACS Chemical Neuroscience, 10(9), pp. 3953-3960. doi: 10.1021/acschemneuro.9b00414en
dc.identifier.doi10.1021/acschemneuro.9b00414en
dc.identifier.eissn1948-7193
dc.identifier.endpage3960en
dc.identifier.issn1948-7193
dc.identifier.issued9en
dc.identifier.journaltitleACS Chemical Neuroscienceen
dc.identifier.startpage3953en
dc.identifier.urihttps://hdl.handle.net/10468/8566
dc.identifier.volume10en
dc.language.isoenen
dc.publisherAmerican Chemical Societyen
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/en
dc.relation.urihttps://pubs.acs.org/doi/10.1021/acschemneuro.9b00414
dc.rights© 2019 American Chemical Society. This document is the Accepted Manuscript version of a Published Work that appeared in final form in ACS Chemical Neuroscience, copyright © American Chemical Society after peer review and technical editing by the publisher. To access the final edited and published work see https://pubs.acs.org/doi/10.1021/acschemneuro.9b00414en
dc.subjectGerm-freeen
dc.subjectMicrobiotaen
dc.subjectSerotoninen
dc.subjectSerotonin 2C receptoren
dc.subjectEditingen
dc.subjectBrainen
dc.titleHost microbiota regulates central nervous system serotonin receptor 2C editing in rodentsen
dc.typeArticle (peer-reviewed)en
Files
Original bundle
Now showing 1 - 2 of 2
Thumbnail Image
Name:
10989_Microbiota_5HT2C_editing_manuscript_revised_.pdf
Size:
680.17 KB
Format:
Adobe Portable Document Format
Description:
Accepted version
Download
Thumbnail Image
Name:
10989_Supporting information revised.pdf
Size:
121.32 KB
Format:
Adobe Portable Document Format
Description:
Supporting information
Download
License bundle
Now showing 1 - 1 of 1
Thumbnail Image
Name:
license.txt
Size:
2.71 KB
Format:
Item-specific license agreed upon to submission
Description:
Download
Collections
Anatomy and Neuroscience - Journal Articles
APC Microbiome Ireland - Journal Articles
Psychiatry - Journal Articles