Chronic intrahippocampal interleukin-1β overexpression in adolescence impairs hippocampal neurogenesis but not neurogenesis-associated cognition

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dc.contributor.author Pawley, Lauren C.
dc.contributor.author Hueston, Cara M.
dc.contributor.author O'Leary, James D.
dc.contributor.author Kozareva, Danka A.
dc.contributor.author Cryan, John F.
dc.contributor.author O'Leary, Olivia F.
dc.contributor.author Nolan, Yvonne M.
dc.date.accessioned 2019-11-18T12:06:22Z
dc.date.available 2019-11-18T12:06:22Z
dc.date.issued 2019-10-08
dc.identifier.citation Pawley, L. C., Hueston, C. M., O'Leary, J. D., Kozareva, D. A., Cryan, J. F., O'Leary, O. F. and Nolan, Y. M. (2019) 'Chronic intrahippocampal interleukin-1β overexpression in adolescence impairs hippocampal neurogenesis but not neurogenesis-associated cognition', Brain, Behavior, and Immunity. doi: 10.1016/j.bbi.2019.10.007 en
dc.identifier.issn 0889-1591
dc.identifier.uri http://hdl.handle.net/10468/9022
dc.identifier.doi 10.1016/j.bbi.2019.10.007 en
dc.description.abstract Both neuroinflammation and adult hippocampal neurogenesis (AHN) are implicated in many neurodegenerative disorders as well as in neuropsychiatric disorders, which often become symptomatic during adolescence. A better knowledge of the impact that chronic neuroinflammation has on the hippocampus during the adolescent period could lead to the discovery of new therapeutics for some of these disorders. The hippocampus is particularly vulnerable to altered concentrations of the pro-inflammatory cytokine interleukin-1β (IL-1β), with elevated levels implicated in the aetiology of neurodegenerative disorders such as Alzheimer’s and Parkinson’s, and stress-related disorders such as depression. The effect of acutely and chronically elevated concentrations of hippocampal IL-1β have been shown to reduce AHN in adult rodents. However, the effect of exposure to chronic overexpression of hippocampal IL-1β during adolescence, a time of increased vulnerability, hasn’t been fully interrogated. Thus, in this study we utilized a lentiviral approach to induce chronic overexpression of IL-1β in the dorsal hippocampus of adolescent male Sprague Dawley rats for 5 weeks, during which time its impact on cognition and hippocampal neurogenesis were examined. A reduction in hippocampal neurogenesis was observed along with a reduced level of neurite branching on hippocampal neurons. However, there was no effect of IL-1β overexpression on performance in pattern separation, novel object recognition or spontaneous alternation in the Y maze. Our study has highlighted that chronic IL-1β overexpression in the hippocampus during the adolescent period exerts a negative impact on neurogenesis independent of cognitive performance, and suggests a degree of resilience of the adolescent hippocampus to inflammatory insult. en
dc.format.mimetype application/pdf en
dc.language.iso en en
dc.publisher Elsevier Inc. en
dc.relation.uri http://www.sciencedirect.com/science/article/pii/S0889159119307603
dc.rights © 2019, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license. en
dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/ en
dc.subject Adolescence en
dc.subject Hippocampus en
dc.subject Neurogenesis en
dc.subject Behavior en
dc.subject Inflammation en
dc.subject IL-1β en
dc.title Chronic intrahippocampal interleukin-1β overexpression in adolescence impairs hippocampal neurogenesis but not neurogenesis-associated cognition 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 2020-10-08
dc.date.updated 2019-11-18T11:57:54Z
dc.description.version Accepted Version en
dc.internal.rssid 499914018
dc.contributor.funder Science Foundation Ireland en
dc.description.status Peer reviewed en
dc.identifier.journaltitle Brain, Behavior, and Immunity en
dc.internal.copyrightchecked Yes
dc.internal.licenseacceptance Yes en
dc.internal.IRISemailaddress y.nolan@ucc.ie en
dc.internal.bibliocheck In press. Check vol / issue / page range. Amend citation as necessary. 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
dc.identifier.eissn 1090-2139


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© 2019, Elsevier Ltd. 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 © 2019, Elsevier Ltd. All rights reserved. This manuscript version is made available under the CC BY-NC-ND 4.0 license.
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