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

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dc.contributor.author van de Wouw, Marcel
dc.contributor.author Stilling, Roman M.
dc.contributor.author Peterson, Veronica L.
dc.contributor.author Ryan, Feargal J.
dc.contributor.author Hoban, Alan E.
dc.contributor.author Shanahan, Fergus
dc.contributor.author Clarke, Gerard
dc.contributor.author Claesson, Marcus J.
dc.contributor.author Dinan, Timothy G.
dc.contributor.author Cryan, John F.
dc.contributor.author Schellekens, Harriët
dc.date.accessioned 2019-09-19T08:45:21Z
dc.date.available 2019-09-19T08:45:21Z
dc.date.issued 2019-08-15
dc.identifier.citation van 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.9b00414 en
dc.identifier.volume 10 en
dc.identifier.issued 9 en
dc.identifier.startpage 3953 en
dc.identifier.endpage 3960 en
dc.identifier.issn 1948-7193
dc.identifier.uri http://hdl.handle.net/10468/8566
dc.identifier.doi 10.1021/acschemneuro.9b00414 en
dc.description.abstract Microbial 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.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher American Chemical Society en
dc.relation.uri https://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.9b00414 en
dc.subject Germ-free en
dc.subject Microbiota en
dc.subject Serotonin en
dc.subject Serotonin 2C receptor en
dc.subject Editing en
dc.subject Brain en
dc.title Host microbiota regulates central nervous system serotonin receptor 2C editing in rodents en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Harriet Schellekens, Biosciences Instittute, University College Cork, Cork, Ireland. +353-21-490-3000 Email: h.schellekens@ucc.ie en
dc.internal.availability Full text available en
dc.check.info Access to this article is restricted until 12 months after publication by request of the publisher. en
dc.check.date 2020-08-15
dc.date.updated 2019-09-19T08:29:46Z
dc.description.version Accepted Version en
dc.internal.rssid 499775470
dc.contributor.funder Science Foundation Ireland en
dc.contributor.funder Mead Johnson Nutrition en
dc.contributor.funder 4D Pharma en
dc.contributor.funder Suntory Foundation en
dc.contributor.funder Nutricia Research Foundation en
dc.description.status Peer reviewed en
dc.identifier.journaltitle ACS Chemical Neuroscience en
dc.internal.copyrightchecked No
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress h.schellekens@ucc.ie en
dc.internal.IRISemailaddress marcel.vandewouw@ucc.ie en
dc.internal.IRISemailaddress f.shanahan@ucc.ie en
dc.internal.IRISemailaddress g.clarke@ucc.ie en
dc.internal.IRISemailaddress m.claesson@ucc.ie en
dc.internal.IRISemailaddress t.dinan@ucc.ie en
dc.internal.IRISemailaddress j.cryan@ucc.ie en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/ en
dc.identifier.eissn 1948-7193


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