The orphan nuclear receptor TLX regulates hippocampal transcriptome changes induced by IL-1β

Show simple item record

dc.contributor.author Ó Léime, Ciarán S.
dc.contributor.author Hoban, Alan E.
dc.contributor.author Hueston, Cara M.
dc.contributor.author Stilling, Roman
dc.contributor.author Moloney, Gerard M.
dc.contributor.author Cryan, John F.
dc.contributor.author Nolan, Yvonne M.
dc.date.accessioned 2018-03-22T14:54:18Z
dc.date.available 2018-03-22T14:54:18Z
dc.date.issued 2018-03-05
dc.identifier.citation Ó Léime, C. S., Hoban, A. E., Hueston, C. M., Stilling, R., Moloney, G., Cryan, J. F. and Nolan, Y. M. (2018) 'The orphan nuclear receptor TLX regulates hippocampal transcriptome changes induced by IL-1β', Brain, Behavior, and Immunity, In Press. doi: 10.1016/j.bbi.2018.03.006 en
dc.identifier.startpage 1 en
dc.identifier.endpage 37 en
dc.identifier.issn 0889-1591
dc.identifier.uri http://hdl.handle.net/10468/5685
dc.identifier.doi 10.1016/j.bbi.2018.03.006
dc.description.abstract TLX is an orphan nuclear receptor highly expressed within neural progenitor cells (NPCs) in the hippocampus where is regulates proliferation. Inflammation has been shown to have negative effects on hippocampal function as well as on NPC proliferation. Specifically, the pro-inflammatory cytokine IL-1β has been shown to suppress NPC proliferation as well as TLX expression in the hippocampus. However, it is unknown whether TLX itself is involved in regulating the inflammatory response in the hippocampus. To explore the role of TLX in inflammation, we assessed changes in the transcriptional landscape of the hippocampus of TLX knockout mice (TLX-/-) compared to wildtype (WT) littermate controls with and without intrahippocampal injection of IL-1β using a whole transcriptome RNA sequencing approach. We demonstrated that there is an increase in the transcription of genes involved in the promotion of inflammation and regulation of cell chemotaxis (Tnf, Il1b, Cxcr1, Cxcr2, Tlr4) and a decrease in the expression of genes relating to synaptic signalling (Lypd1, Syt4, Cplx2) in cannulated TLX-/- mice compared to WT controls. We demonstrate that mice lacking in TLX share a similar increase in 176 genes involved in regulating inflammation (e.g. Cxcl1, Tnf, Il1b) as WT mice injected with IL-1β into the hippocampus. Moreover, TLX-/- mice injected with IL-1β display a blunted transcriptional profile compared to WT mice injected with IL-1β. Thus, TLX-/- mice, which already have an exaggerated inflammatory profile after cannulation surgery, are primed to respond differently to an inflammatory stimulus such as IL-1β. Together, these results demonstrate that TLX regulates hippocampal inflammatory transcriptome response to brain injury (in this case cannulation surgery) and cytokine stimulation. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0889159118300503
dc.rights © 2018 Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. en
dc.rights.uri http://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject RNA sequencing en
dc.subject TLX en
dc.subject Interleukin-1 beta en
dc.subject Hippocampus en
dc.subject Neuroinflammation en
dc.subject Nuclear receptors en
dc.title The orphan nuclear receptor TLX regulates hippocampal transcriptome changes induced by IL-1β en
dc.type Article (peer-reviewed) en
dc.internal.authorcontactother Yvonne Nolan, Department Of Anatomy & Neuroscience, University College Cork, Cork, Ireland. +353-21-490-3000 Email: y.nolan@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 2019-03-05
dc.date.updated 2018-03-22T14:48:30Z
dc.description.version Accepted Version en
dc.internal.rssid 430915038
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Brain, Behavior, and Immunity en
dc.internal.copyrightchecked No !!CORA!! en
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress y.nolan@ucc.ie en
dc.internal.bibliocheck In Press, check and update citation volume start and end page en
dc.relation.project info:eu-repo/grantAgreement/SFI/SFI Investigator Programme/12/IA/1537/IE/The nuclear receptor TLX as a cell intrinsic regulator underlying inflammation and stress-induced changes in hippocampal neurogenesis: relevance to cognitive disorders/ en


Files in this item

This item appears in the following Collection(s)

Show simple item record

© 2018 Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license. Except where otherwise noted, this item's license is described as © 2018 Elsevier Inc. All rights reserved. This manuscript version is made available under the CC-BY-NC-ND 4.0 license.
This website uses cookies. By using this website, you consent to the use of cookies in accordance with the UCC Privacy and Cookies Statement. For more information about cookies and how you can disable them, visit our Privacy and Cookies statement