dc.contributor.author	Hoban, Alan E.
dc.contributor.author	Stilling, Roman M.
dc.contributor.author	Ryan, Feargal J.
dc.contributor.author	Shanahan, Fergus
dc.contributor.author	Dinan, Timothy G.
dc.contributor.author	Claesson, Marcus J.
dc.contributor.author	Clarke, Gerard
dc.contributor.author	Cryan, John F.
dc.contributor.funder	Science Foundation Ireland	en
dc.contributor.funder	Irish Research Council	en
dc.contributor.funder	Department of Agriculture, Food and the Marine	en
dc.contributor.funder	Enterprise Ireland	en
dc.contributor.funder	National Alliance for Research on Schizophrenia and Depression	en
dc.contributor.funder	Health Research Board	en
dc.date.accessioned	2019-11-01T07:27:44Z
dc.date.available	2019-11-01T07:27:44Z
dc.date.issued	2016-04-05
dc.description.abstract	The prefrontal cortex (PFC) is a key region implicated in a range of neuropsychiatric disorders such as depression, schizophrenia and autism. In parallel, the role of the gut microbiota in contributing to these disorders is emerging. Germ-free (GF) animals, microbiota-deficient throughout life, have been instrumental in elucidating the role of the microbiota in many aspects of physiology, especially the role of the microbiota in anxiety-related behaviours, impaired social cognition and stress responsivity. Here we aim to further elucidate the mechanisms of the microbial influence by investigating changes in the homeostatic regulation of neuronal transcription of GF mice within the PFC using a genome-wide transcriptome profiling approach. Our results reveal a marked, concerted upregulation of genes linked to myelination and myelin plasticity. This coincided with upregulation of neural activity-induced pathways, potentially driving myelin plasticity. Subsequent investigation at the ultrastructural level demonstrated the presence of hypermyelinated axons within the PFC of GF mice. Notably, these changes in myelin and activity-related gene expression could be reversed by colonization with a conventional microbiota following weaning. In summary, we believe we demonstrate for the first time that the microbiome is necessary for appropriate and dynamic regulation of myelin-related genes with clear implications for cortical myelination at an ultrastructural level. The microbiota is therefore a potential therapeutic target for psychiatric disorders involving dynamic myelination in the PFC.	en
dc.description.sponsorship	Irish Research Council (Grant Number GOIPD/2014/355); NARSAD (Grant Number 20771)	en
dc.description.status	Peer reviewed	en
dc.description.version	Published Version	en
dc.format.mimetype	application/pdf	en
dc.identifier.articleid	e774	en
dc.identifier.citation	Hoban, A. E., Stilling, R. M., Ryan, F. J., Shanahan, F., Dinan, T. G., Claesson, M. J., Clarke, G. and Cryan, J. F. (2016) 'Regulation of prefrontal cortex myelination by the microbiota', Translational Psychiatry, 6(4), e774. (9pp.) DOI: 10.1038/tp.2016.42	en
dc.identifier.doi	10.1038/tp.2016.42	en
dc.identifier.eissn	2158-3188
dc.identifier.endpage	9	en
dc.identifier.issued	4	en
dc.identifier.journaltitle	Translational Psychiatry	en
dc.identifier.startpage	1	en
dc.identifier.uri	https://hdl.handle.net/10468/8932
dc.identifier.volume	6	en
dc.language.iso	en	en
dc.publisher	Nature Publishing Group	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.relation.uri	https://www.nature.com/articles/tp201642
dc.rights	© The Author(s) 2016. This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/	en
dc.rights.uri	http://creativecommons.org/licenses/by/4.0/	en
dc.subject	Microbiota	en
dc.subject	Prefrontal cortex	en
dc.subject	Molecular neuroscience	en
dc.subject	Psychiatric disorder	en
dc.title	Regulation of prefrontal cortex myelination by the microbiota	en
dc.type	Article (peer-reviewed)	en

Regulation of prefrontal cortex myelination by the microbiota

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