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Unmoving and uninflamed: characterizing neuroinflammatory dysfunction in the Wistar‐Kyoto rat model of depression

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dc.contributor.authorFarinha Ferreira, Jorge Miguel
dc.contributor.authorMagalhães, Daniela M
dc.contributor.authorNeuparth-Sottomayor, Mariana
dc.contributor.authorRafael, H.
dc.contributor.authorMiranda-Lourenço, Catarina
dc.contributor.authorSebastião, Ana M
dc.date.accessioned2025-02-07T12:36:46Z
dc.date.available2025-02-07T12:36:46Z
dc.date.issued2024
dc.description© 2024 The Authors. Journal of Neurochemistry published by John Wiley & Sons Ltd on behalf of International Society for Neurochemistry. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.pt_PT
dc.description.abstractReductionistic research on depressive disorders has been hampered by the limitations of animal models. Recently, it has been hypothesized that neuroinflammation is a key player in depressive disorders. The Wistar-Kyoto (WKY) rat is an often-used animal model of depression, but no information so far exists on its neuroinflammatory profile. As such, we compared male young adult WKY rats to Wistar (WS) controls, with regard to both behavioral performance and brain levels of key neuroinflammatory markers. We first assessed anxiety- and depression-like behaviors in a battery consisting of the Elevated Plus Maze (EPM), the Novelty Suppressed Feeding (NSFT), Open Field (OFT), Social Interaction (SIT), Forced Swim (FST), Sucrose Preference (SPT), and Splash tests (ST). We found that WKY rats displayed increased NSFT feeding latency, decreased OFT center zone permanence, decreased EPM open arm permanence, decreased SIT interaction time, and increased immobility in the FST. However, WKY rats also evidenced marked hypolocomotion, which is likely to confound performance in such tests. Interestingly, WKY rats performed similarly, or even above, to WS levels in the SPT and ST, in which altered locomotion is not a significant confound. In a separate cohort, we assessed prefrontal cortex (PFC), hippocampus and amygdala levels of markers of astrocytic (GFAP, S100A10) and microglial (Iba1, CD86, Ym1) activation status, as well as of three key proinflammatory cytokines (IL-1β, IL-6, TNF-α). There were no significant differences between strains in any of these markers, in any of the regions assessed. Overall, results highlight that behavioral data obtained with WKY rats as a model of depression must be carefully interpreted, considering the marked locomotor activity deficits displayed. Furthermore, our data suggest that, despite WKY rats replicating many depression-associated neurobiological alterations, as shown by others, this is not the case for neuroinflammation-related alterations, thus representing a novel limitation of this model.pt_PT
dc.description.sponsorshipThis work was supported by project funding from Fundação para a Ciência e para a Tecnologia (FCT) to AMS (PTDC/MED-FAR/4834/2021). This project has received funding from H2020-WIDESPREAD-05-2017-Twinning (EpiEpinet) under grant agreement No. 952455. MF-F (SFRH/BD/147505/2019), DMM (PD/BD/128405/2017), and CM-L (SFRH/BD/118238/2016) were supported by PhD fellowships from FCT. MN-S was in receipt of a fellowship from FCT (IMM/BI/36-2022).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationJ Neurochem. 2024 Sep;168(9):2443-2460pt_PT
dc.identifier.doi10.1111/jnc.16083pt_PT
dc.identifier.eissn1471-4159
dc.identifier.issn0022-3042
dc.identifier.urihttp://hdl.handle.net/10400.5/98186
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherWileypt_PT
dc.relationIMM/BI/36-2022pt_PT
dc.relationEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
dc.relationLess may be more: potential procognitive and antidepressant effects of sub-hallucinogenic psilocybin doses in an animal model of depression
dc.relationNot available
dc.relation.publisherversionhttps://onlinelibrary.wiley.com/journal/14714159pt_PT
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/pt_PT
dc.subjectWistar‐Kyotopt_PT
dc.subjectAnxietypt_PT
dc.subjectDepressionpt_PT
dc.subjectNeuroinflammationpt_PT
dc.titleUnmoving and uninflamed: characterizing neuroinflammatory dysfunction in the Wistar‐Kyoto rat model of depressionpt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleEpileptogenesis and Epilepsy Network: from genes, synapses and circuits to pave the way for novel drugs and strategies
oaire.awardTitleLess may be more: potential procognitive and antidepressant effects of sub-hallucinogenic psilocybin doses in an animal model of depression
oaire.awardTitleNot available
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/Concurso de Projetos IC&DT em Todos os Domínios Científicos/PTDC%2FMED-FAR%2F4834%2F2021/PT
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/952455/EU
oaire.awardURIinfo:eu-repo/grantAgreement/FCT//SFRH%2FBD%2F147505%2F2019/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/PD%2FBD%2F128405%2F2017/PT
oaire.awardURIinfo:eu-repo/grantAgreement/FCT/OE/SFRH%2FBD%2F118238%2F2016/PT
oaire.citation.endPage2460pt_PT
oaire.citation.issue9pt_PT
oaire.citation.startPage2443pt_PT
oaire.citation.titleJournal of Neurochemistrypt_PT
oaire.citation.volume168pt_PT
oaire.fundingStreamConcurso de Projetos IC&DT em Todos os Domínios Científicos
oaire.fundingStreamH2020
oaire.fundingStreamOE
oaire.fundingStreamOE
person.familyNameFarinha Ferreira
person.familyNameMelo Magalhães
person.familyNameSerra de Sequeira Neuparth Sottomayor
person.familyNameMarques Simões
person.familyNameMiranda Lourenço
person.familyNameSebastião
person.givenNameJorge Miguel
person.givenNameDaniela Cristina
person.givenNameMariana
person.givenNameHugo Rafael
person.givenNameCatarina
person.givenNameAna M
person.identifier.ciencia-idE416-A9B5-8059
person.identifier.ciencia-idAC19-5A99-46A9
person.identifier.ciencia-id6B1E-0623-D291
person.identifier.ciencia-id5D10-565E-DB86
person.identifier.ciencia-idA815-F59B-47E2
person.identifier.ciencia-idF112-55E8-E37E
person.identifier.orcid0000-0003-1240-0717
person.identifier.orcid0000-0002-1662-2002
person.identifier.orcid0000-0002-2309-0171
person.identifier.orcid0000-0002-9479-5355
person.identifier.orcid0000-0002-9633-7999
person.identifier.orcid0000-0001-9030-6115
person.identifier.scopus-author-id7004409879
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.identifierhttp://doi.org/10.13039/501100001871
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameEuropean Commission
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
project.funder.nameFundação para a Ciência e a Tecnologia
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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