Microbial regulation of microRNA expression in the amygdala and prefrontal cortex

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dc.contributor.authorHoban, Alan E.
dc.contributor.authorStilling, Roman M.
dc.contributor.authorMoloney, Gerard M.
dc.contributor.authorMoloney, Rachel D.
dc.contributor.authorShanahan, Fergus
dc.contributor.authorDinan, Timothy G.
dc.contributor.authorCryan, John F.
dc.contributor.authorClarke, Gerard
dc.contributor.funderScience Foundation Ireland
dc.contributor.funderIrish Research Council
dc.contributor.funderHealth Research Board
dc.contributor.funderDepartment of Agriculture, Food and the Marine
dc.contributor.funderMead Johnson Nutrition
dc.contributor.funderCremo
dc.contributor.funderSuntory Foundation
dc.contributor.funderNutricia Research Foundation
dc.contributor.funder4D Pharma
dc.contributor.funderBrain and Behavior Research Foundation
dc.contributor.funderEnterprise Ireland
dc.date.accessioned2017-09-26T11:39:23Z
dc.date.available2017-09-26T11:39:23Z
dc.date.issued2017
dc.description.abstractBackground: There is growing evidence for a role of the gut microbiome in shaping behaviour relevant to many psychiatric and neurological disorders. Preclinical studies using germ-free (GF) animals have been essential in contributing to our current understanding of the potential importance of the host microbiome for neurodevelopment and behaviour. In particular, it has been repeatedly demonstrated that manipulation of the gut microbiome modulates anxiety-like behaviours. The neural circuits that underlie anxiety-and fear-related behaviours are complex and heavily depend on functional communication between the amygdala and prefrontal cortex (PFC). Previously, we have shown that the transcriptional networks within the amygdala and PFC of GF mice are altered. MicroRNAs (miRNAs) act through translational repression to control gene translation and have also been implicated in anxiety-like behaviours. However, it is unknown whether these features of host post-transcriptional machinery are also recruited by the gut microbiome to exert control over CNS transcriptional networks. Results: We conducted Illumina (R) next-generation sequencing (NGS) in the amygdala and PFC of conventional, GF and germ-free colonized mice (exGF). We found a large proportion of miRNAs to be dysregulated in GF animals in both brain regions (103 in the amygdala and 31 in the PFC). Additionally, colonization of GF mice normalized some of the noted alterations. Next, we used a complementary approach to GF by manipulating the adult rat microbiome with an antibiotic cocktail to deplete the gut microbiota and found that this strategy also impacted the expression of relevant miRNAs. Conclusion: These results suggest that the microbiome is necessary for appropriate regulation of miRNA expression in brain regions implicated in anxiety-like behaviours.en
dc.description.sponsorshipBrian and Behaviour Research Foundation (NARSAD Young Investigator Grant (20771, HRB: HRA_POR/2012/32); Science Foundation Ireland (SFI) (SFI/12/RC/2273); Irish Research Council (Government of Ireland Postdoctoral Fellowship (GOIPD/2014/355)en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid102
dc.identifier.citationHoban, A. E., Stilling, R. M., M. Moloney, G., Moloney, R. D., Shanahan, F., Dinan, T. G., Cryan, J. F. and Clarke, G. (2017) 'Microbial regulation of microRNA expression in the amygdala and prefrontal cortex', Microbiome, 5(1), 102 (11pp). doi: 10.1186/s40168-017-0321-3en
dc.identifier.doi10.1186/s40168-017-0321-3
dc.identifier.issn2049-2618
dc.identifier.journaltitleMicrobiomeen
dc.identifier.urihttps://hdl.handle.net/10468/4808
dc.identifier.volume5
dc.language.isoenen
dc.publisherBiomed Central Ltden
dc.relation.projectinfo:eu-repo/grantAgreement/SFI/SFI Research Centres/12/RC/2273/IE/Alimentary Pharmabiotic Centre (APC) - Interfacing Food & Medicine/
dc.relation.urihttps://microbiomejournal.biomedcentral.com/articles/10.1186/s40168-017-0321-3
dc.rights© 2017, the Authors. Open Access. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.en
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/
dc.subjectAmygdalaen
dc.subjectPrefrontal cortexen
dc.subjectMicrobiome gut brain axisen
dc.subjectMicroRNAsen
dc.subjectGerm freeen
dc.subjectAntibioticsen
dc.subjectmiR-206-3pen
dc.subjectGut brain axisen
dc.subjectNeurotrophic factoren
dc.subjectGene expressionen
dc.subjectNeural circuitsen
dc.subjectBehavioren
dc.subjectMiceen
dc.subjectAnxietyen
dc.subjectStressen
dc.subjectModelen
dc.subjectRaten
dc.titleMicrobial regulation of microRNA expression in the amygdala and prefrontal cortexen
dc.typeArticle (peer-reviewed)en
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