Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | eng |
| Título da fonte: | Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
| Texto Completo: | http://hdl.handle.net/10451/52077 |
Resumo: | © 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/). |
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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 processes5-HT receptorsFemale aggressionGlycogen synthase kinase-3 β (GSK-3β)MyelinationPredation stressTryptophan hydroxylase-2 (Tph2)© 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/).The 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.The 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.).MDPIRepositório da Universidade de LisboaSvirin, EvgeniyVeniaminova, EkaterinaNunes, JoãoGorlova, AnnaUmriukhin, AlekseiKalueff, Allan V.Proshin, AndreyAnthony, Daniel C.Nedorubov, AndreyTse, Anna Chung KwanWalitza, SusanneLim, Lee WeiLesch, Klaus-PeterStrekalova, Tatyana2022-03-29T16:08:01Z20222022-01-01T00:00:00Zinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleapplication/pdfhttp://hdl.handle.net/10451/52077engCells. 2022 Mar 18;11(6):103610.3390/cells110610362073-4409info:eu-repo/semantics/openAccessreponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãoinstacron:RCAAP2023-11-08T16:57:05Zoai:repositorio.ul.pt:10451/52077Portal AgregadorONGhttps://www.rcaap.pt/oai/openaireopendoar:71602024-03-19T22:03:12.492080Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informaçãofalse |
| dc.title.none.fl_str_mv |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| title |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| spellingShingle |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes Svirin, Evgeniy 5-HT receptors Female aggression Glycogen synthase kinase-3 β (GSK-3β) Myelination Predation stress Tryptophan hydroxylase-2 (Tph2) |
| title_short |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| title_full |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| title_fullStr |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| title_full_unstemmed |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| title_sort |
Predation stress causes excessive aggression in female mice with partial genetic inactivation of Tryptophan hydroxylase-2: evidence for altered myelination-related processes |
| author |
Svirin, Evgeniy |
| author_facet |
Svirin, Evgeniy Veniaminova, Ekaterina Nunes, João Gorlova, Anna Umriukhin, Aleksei Kalueff, Allan V. Proshin, Andrey Anthony, Daniel C. Nedorubov, Andrey Tse, Anna Chung Kwan Walitza, Susanne Lim, Lee Wei Lesch, Klaus-Peter Strekalova, Tatyana |
| author_role |
author |
| author2 |
Veniaminova, Ekaterina Nunes, João Gorlova, Anna Umriukhin, Aleksei Kalueff, Allan V. Proshin, Andrey Anthony, Daniel C. Nedorubov, Andrey Tse, Anna Chung Kwan Walitza, Susanne Lim, Lee Wei Lesch, Klaus-Peter Strekalova, Tatyana |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Repositório da Universidade de Lisboa |
| dc.contributor.author.fl_str_mv |
Svirin, Evgeniy Veniaminova, Ekaterina Nunes, João Gorlova, Anna Umriukhin, Aleksei Kalueff, Allan V. Proshin, Andrey Anthony, Daniel C. Nedorubov, Andrey Tse, Anna Chung Kwan Walitza, Susanne Lim, Lee Wei Lesch, Klaus-Peter Strekalova, Tatyana |
| dc.subject.por.fl_str_mv |
5-HT receptors Female aggression Glycogen synthase kinase-3 β (GSK-3β) Myelination Predation stress Tryptophan hydroxylase-2 (Tph2) |
| topic |
5-HT receptors Female aggression Glycogen synthase kinase-3 β (GSK-3β) Myelination Predation stress Tryptophan hydroxylase-2 (Tph2) |
| 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/). |
| publishDate |
2022 |
| dc.date.none.fl_str_mv |
2022-03-29T16:08:01Z 2022 2022-01-01T00:00:00Z |
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info:eu-repo/semantics/publishedVersion |
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info:eu-repo/semantics/article |
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article |
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publishedVersion |
| dc.identifier.uri.fl_str_mv |
http://hdl.handle.net/10451/52077 |
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http://hdl.handle.net/10451/52077 |
| dc.language.iso.fl_str_mv |
eng |
| language |
eng |
| dc.relation.none.fl_str_mv |
Cells. 2022 Mar 18;11(6):1036 10.3390/cells11061036 2073-4409 |
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info:eu-repo/semantics/openAccess |
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openAccess |
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application/pdf |
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MDPI |
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MDPI |
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reponame:Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) instname:Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação instacron:RCAAP |
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Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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RCAAP |
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RCAAP |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) |
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Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos) - Agência para a Sociedade do Conhecimento (UMIC) - FCT - Sociedade da Informação |
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