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

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dc.contributor.authorÓ Léime, Ciarán S.
dc.contributor.authorHoban, Alan E.
dc.contributor.authorHueston, Cara M.
dc.contributor.authorStilling, Roman
dc.contributor.authorMoloney, Gerard M.
dc.contributor.authorCryan, John F.
dc.contributor.authorNolan, Yvonne M.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2018-03-22T14:54:18Z
dc.date.available2018-03-22T14:54:18Z
dc.date.issued2018-03-05
dc.date.updated2018-03-22T14:48:30Z
dc.description.abstractTLX 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.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationÓ 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.2018.03.006en
dc.identifier.doi10.1016/j.bbi.2018.03.006
dc.identifier.endpage37en
dc.identifier.issn0889-1591
dc.identifier.journaltitleBrain, Behavior, and Immunityen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/5685
dc.language.isoenen
dc.publisherElsevieren
dc.relation.projectinfo: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
dc.relation.urihttp://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.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en
dc.subjectRNA sequencingen
dc.subjectTLXen
dc.subjectInterleukin-1 betaen
dc.subjectHippocampusen
dc.subjectNeuroinflammationen
dc.subjectNuclear receptorsen
dc.titleThe orphan nuclear receptor TLX regulates hippocampal transcriptome changes induced by IL-1βen
dc.typeArticle (peer-reviewed)en
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