Deletion of TLX and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampus

dc.contributor.authorKozareva, Danka A.
dc.contributor.authorO'Leary, Olivia F.
dc.contributor.authorCryan, John F.
dc.contributor.authorNolan, Yvonne M.
dc.contributor.funderScience Foundation Irelanden
dc.date.accessioned2017-10-09T11:30:36Z
dc.date.available2017-10-09T11:30:36Z
dc.date.issued2017-10-03
dc.date.updated2017-10-09T11:21:17Z
dc.description.abstractAdolescence is a sensitive period of neurodevelopment during which life experiences and the surrounding environment can have profound effects on the brain. Neurogenesis is a neurodevelopmental process of generating functional neurons from neural stem cells. Hippocampal neurogenesis occurs throughout the lifespan and has been shown to play a role in learning, memory and in mood regulation. In adulthood it is influenced by extrinsic environmental factors such as exercise and stress. Intrinsic factors that regulate hippocampal neurogenesis include the orphan nuclear receptor TLX (Nr2e1) which is primarily expressed in the neurogenic niches of the brain. While mechanisms regulating adult hippocampal neurogenesis have been widely studied, less is known on how hippocampal neurogenesis is affected during adolescence. Thus, the aim of this study was to investigate the influence of both TLX and isolation stress on exercise-induced increases in neurogenesis in running and sedentary conditions during adolescence. Single- (i.e. isolation stress) wild type and Nr2e1-/- or pair-housed wild type mice were housed in sedentary conditions or allowed free access to running wheels for 3 weeks during the adolescent period. A reduction of neuronal survival was evident in mice lacking TLX, and exercise did not increase hippocampal neurogenesis in these Nr2e1-/- mice. This suggests that TLX is necessary for the pro-neurogenic effects of exercise during adolescence. Interestingly, although social isolation during adolescence did not affect hippocampal neurogenesis, it prevented an exercise-induced increase in neurogenesis in the ventral hippocampus. Together these data demonstrate the importance of intrinsic and extrinsic factors in promoting an exercise-induced increase in neurogenesis at this key point in life. This article is protected by copyright. All rights reserved.en
dc.description.statusPeer revieweden
dc.description.versionAccepted Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.citationKozareva, D. A., O'Leary, O. F., Cryan, J. F. and Nolan, Y. M. 'Deletion of TLX and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampus', Hippocampus, In Press. doi: 10.1002/hipo.22805en
dc.identifier.doi10.1002/hipo.22805
dc.identifier.endpage27en
dc.identifier.issn1098-1063
dc.identifier.journaltitleHippocampusen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/4846
dc.language.isoenen
dc.publisherWileyen
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.rights© 2017 John Wiley & Sons, Inc.This is the peer reviewed version of the following article: Kozareva, D. A., O'Leary, O. F., Cryan, J. F. and Nolan, Y. M., Deletion of Tlx and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampus. Hippocampus. Accepted Author Manuscript. which has been published in final form at http://dx.doi.org/10.1002/hipo.22805. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving.en
dc.subjectAdult neurogenesisen
dc.subjectAdolescenceen
dc.subjectStressen
dc.subjectExerciseen
dc.subjectTLXen
dc.titleDeletion of TLX and social isolation impairs exercise-induced neurogenesis in the adolescent hippocampusen
dc.typeArticle (peer-reviewed)en
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