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Age-related impact of social isolation in mice: young vs middle-aged

dc.contributor.authorMagalhães, Daniela M
dc.contributor.authorMampay, Myrthe
dc.contributor.authorSebastião, Ana M
dc.contributor.authorSheridan, Graham K.
dc.contributor.authorValente, Cláudia A.
dc.date.accessioned2025-06-12T14:00:38Z
dc.date.available2025-06-12T14:00:38Z
dc.date.issued2024
dc.descriptionCopyright © 2024 Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)pt_PT
dc.description.abstractSocial isolation is a chronic mild stressor and a significant risk factor for mental health disorders. Herein we explored the impact of social isolation on depression- and anxiety-like behaviours, as well as spatial memory impairments, in middle-aged male mice compared to post-weaning mice. We aimed to quantify and correlate social isolation-induced behaviour discrepancies with changes in hippocampal glial cell reactivity and pro-inflammatory cytokine levels. Post-weaning and middle-aged C57BL7/J6 male mice were socially isolated for a 3-week period and behavioural tests were performed on the last five days of isolation. We found that 3 weeks of social isolation led to depressive-like behaviour in the forced swim test, anxiety-like behaviour in the open field test, and spatial memory impairment in the Morris water maze paradigm in middle-aged male mice. These behavioural alterations were not observed in male mice after post-weaning social isolation, indicating resilience to isolation-mediated stress. Increased Iba-1 expression and NLRP3 priming were both observed in the hippocampus of socially isolated middle-aged mice, suggesting a role for microglia and NLRP3 pathway in the detrimental effects of social isolation on cognition and behaviour. Young socially isolated mice also demonstrated elevated NLRP3 priming compared to controls, but no differences in Iba-1 levels and no significant changes in behaviour. Ageing-induced microglia activation and enhancement of IL-1β, TNF-α and IL-6 proinflammatory cytokines, known signs of a chronic low-grade inflammatory state, were also detected. Altogether, data suggest that social isolation, in addition to inflammaging, contributes to stress-related cognitive impairment in middle-aged mice.pt_PT
dc.description.sponsorshipThe work received funding from the European Union's Horizon 2020 research and innovation programme [Grant agreement 952455] and Project [PTDC/MED-NEU/6954/2020] from Fundação para a Ciência e a Tecnologia (FCT), Portugal. D.M.M. was supported by a PhD scholarship from FCT [PD/BD/128405/2017]. G.K.S. is grateful for support from the Leverhulme Trust [RPG-2018-443], United Kingdom.pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationNeurochem Int. 2024 Mar:174:105678pt_PT
dc.identifier.doi10.1016/j.neuint.2024.105678pt_PT
dc.identifier.eissn1872-9754
dc.identifier.issn0197-0186
dc.identifier.urihttp://hdl.handle.net/10400.5/101535
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherElsevierpt_PT
dc.relationPTDC/MED-NEU/6954/2020pt_PT
dc.relationEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
dc.relation.publisherversionhttps://www.sciencedirect.com/journal/neurochemistry-internationalpt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectBehaviourpt_PT
dc.subjectHippocampuspt_PT
dc.subjectInflammagingpt_PT
dc.subjectNeuroinflammationpt_PT
dc.subjectSocial isolationpt_PT
dc.titleAge-related impact of social isolation in mice: young vs middle-agedpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardNumber952455
oaire.awardNumberPD/BD/128405/2017
oaire.awardTitleEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/952455/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//PD%2FBD%2F128405%2F2017/PT
oaire.citation.titleNeurochemistry Internationalpt_PT
oaire.citation.volume174pt_PT
oaire.fundingStreamH2020
person.familyNameMelo Magalhães
person.familyNameSebastião
person.familyNameValente
person.givenNameDaniela Cristina
person.givenNameAna M
person.givenNameCláudia
person.identifier.ciencia-idAC19-5A99-46A9
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.ciencia-idBD1B-6720-D51D
person.identifier.orcid0000-0002-1662-2002
person.identifier.orcid0000-0001-9030-6115
person.identifier.orcid0000-0001-5405-3130
person.identifier.ridA-3868-2013
person.identifier.scopus-author-id7004409879
person.identifier.scopus-author-id9842734300
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
relation.isAuthorOfPublicationf5ea0376-9ad8-4f96-b2b8-87c0ea4ede76
relation.isAuthorOfPublication304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isAuthorOfPublicationf8ed7487-bd16-460b-9e4f-ef0ca623b5ba
relation.isAuthorOfPublication.latestForDiscovery304abd7f-071b-4447-a8a3-4aa5f0547141
relation.isProjectOfPublication71376ce5-3732-4d41-b053-3dad707d6191
relation.isProjectOfPublication23290798-7154-421e-a4f1-0183db14534e
relation.isProjectOfPublication.latestForDiscovery71376ce5-3732-4d41-b053-3dad707d6191

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