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Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes

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dc.contributor.authorSvirin, Evgeniy
dc.contributor.authorVeniaminova, Ekaterina
dc.contributor.authorNunes, João
dc.contributor.authorGorlova, Anna
dc.contributor.authorUmriukhin, Aleksei
dc.contributor.authorKalueff, Allan V.
dc.contributor.authorProshin, Andrey
dc.contributor.authorAnthony, Daniel C.
dc.contributor.authorNedorubov, Andrey
dc.contributor.authorTse, Anna Chung Kwan
dc.contributor.authorWalitza, Susanne
dc.contributor.authorLim, Lee Wei
dc.contributor.authorLesch, Klaus-Peter
dc.contributor.authorStrekalova, Tatyana
dc.date.accessioned2022-03-29T16:08:01Z
dc.date.available2022-03-29T16:08:01Z
dc.date.issued2022
dc.description© 2022 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).pt_PT
dc.description.abstractThe interaction between brain serotonin (5-HT) deficiency and environmental adversity may predispose females to excessive aggression. Specifically, complete inactivation of the gene encoding tryptophan hydroxylase-2 (Tph2) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (Tph2-/-) mice. In heterozygous male mice (Tph2+/-), there is a moderate reduction in brain 5-HT levels, and when they are exposed to stress, they exhibit increased aggression. Here, we exposed female Tph2+/- mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. Tph2+/- females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors Htr1a and Htr2a, glycogen synthase kinase-3 β (GSK-3β), and c-fos as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (Mbp), proteolipid protein 1 (Plp1), myelin-associated glycoprotein (Mag), and myelin oligodendrocyte glycoprotein (Mog). The expression of the plasticity markers synaptophysin (Syp) and cAMP response element binding protein (Creb), but not AMPA receptor subunit A2 (GluA2), were affected by genotype. Moreover, in a separate experiment, naïve female Tph2+/- mice showed signs of enhanced stress resilience in the modified swim test with repeated swimming sessions. Taken together, the combination of a moderate reduction in brain 5-HT with environmental challenges results in behavioral changes in female mice that resemble the aggression-related behavior and resilience seen in stressed male mutants; additionally, the combination is comparable to the phenotype of null mutants lacking neuronal 5-HT. Changes in myelination-associated processes are suspected to underpin the molecular mechanisms leading to aggressive behavior.pt_PT
dc.description.sponsorshipThe authors’ animal work reported here was supported by Deutsche Forschungsgemeinschaft (DFG:CRC TRR58A1/A5), the European Union’s Seventh Framework Programme (FP7/2007–2013) under Grant No. 602805 (Aggressotype), the Horizon 2020 Research and Innovation Programme under Grant No. 728018 (Eat2beNice) (to K.-P.L. and T.S.) and Grant No. 101007642 (PhytoAPP) (to D.C.A. and T.S.), and Swiss-Russian Cooperation grant RPG Russia 2020 (to S.W. and K.-P.L.). Molecular data analysis was supported by RAS N0520-2019-0031 (to E.S. and T.S.).pt_PT
dc.description.versioninfo:eu-repo/semantics/publishedVersionpt_PT
dc.identifier.citationCells. 2022 Mar 18;11(6):1036pt_PT
dc.identifier.doi10.3390/cells11061036pt_PT
dc.identifier.eissn2073-4409
dc.identifier.urihttp://hdl.handle.net/10451/52077
dc.language.isoengpt_PT
dc.peerreviewedyespt_PT
dc.publisherMDPIpt_PT
dc.relationAggression subtyping for improved insight and treatment innovation in psychiatric disorders
dc.relationEffects of Nutrition and Lifestyle on Impulsive, Compulsive, and Externalizing behaviours
dc.relationINNOVATIVE WATER-SOLUBLE PHYTOMATERIAL INHIBITORs FOR ALZHEIMERs AND PARKINSONs DISEASES PREVENTION
dc.relation.publisherversionhttps://www.mdpi.com/journal/cellspt_PT
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/pt_PT
dc.subject5-HT receptorspt_PT
dc.subjectFemale aggressionpt_PT
dc.subjectGlycogen synthase kinase-3 β (GSK-3β)pt_PT
dc.subjectMyelinationpt_PT
dc.subjectPredation stresspt_PT
dc.subjectTryptophan hydroxylase-2 (Tph2)pt_PT
dc.titlePredation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processespt_PT
dc.typejournal article
dspace.entity.typePublication
oaire.awardTitleAggression subtyping for improved insight and treatment innovation in psychiatric disorders
oaire.awardTitleEffects of Nutrition and Lifestyle on Impulsive, Compulsive, and Externalizing behaviours
oaire.awardTitleINNOVATIVE WATER-SOLUBLE PHYTOMATERIAL INHIBITORs FOR ALZHEIMERs AND PARKINSONs DISEASES PREVENTION
oaire.awardURIinfo:eu-repo/grantAgreement/EC/FP7/602805/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/728018/EU
oaire.awardURIinfo:eu-repo/grantAgreement/EC/H2020/101007642/EU
oaire.citation.issue6pt_PT
oaire.citation.titleCellspt_PT
oaire.citation.volume11pt_PT
oaire.fundingStreamFP7
oaire.fundingStreamH2020
oaire.fundingStreamH2020
person.familyNameda Costa Alvares Viegas Nunes
person.givenNameJoão Pedro
person.identifierQ-8648-2017
person.identifier.ciencia-idF413-C6F8-AFF1
person.identifier.orcid0000-0003-0127-5420
person.identifier.scopus-author-id55974674700
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.identifierhttp://doi.org/10.13039/501100008530
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
project.funder.nameEuropean Commission
rcaap.rightsopenAccesspt_PT
rcaap.typearticlept_PT
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relation.isAuthorOfPublication.latestForDiscovery571fa049-46ca-4e54-b555-23993a7e78ca
relation.isProjectOfPublication76a52147-6d72-4687-b631-22a7a7b66314
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