Saved in:
Bibliografiske detaljer
Main Authors: Svirin, Evgeniy, Veniaminova, Ekaterina, Costa-Nunes, João Pedro, Gorlova, Anna, Umryukhin, Aleksey, Kalueff, Allan, A.T., Proshin, Anthony, Daniel, Недорубов, Андрей Анатольевич, Chung Kwan Tse, Anna, Walitza, Susanne, Lim, Lee Wei, Lesch, Klaus-Peter, Strekalova, Tatyana
Format: Recurso digital
Sprog:engelsk
Udgivet: Zenodo 2022
Fag:
Online adgang:https://doi.org/10.3390/cells11061036
Tags: Tilføj Tag
Ingen Tags, Vær først til at tagge denne postø!
_version_ 1866901841103552512
author Svirin, Evgeniy
Veniaminova, Ekaterina
Costa-Nunes, João Pedro
Gorlova, Anna
Umryukhin, Aleksey
Kalueff, Allan
A.T., Proshin
Anthony, Daniel
Недорубов, Андрей Анатольевич
Chung Kwan Tse, Anna
Walitza, Susanne
Lim, Lee Wei
Lesch, Klaus-Peter
Strekalova, Tatyana
author_facet Svirin, Evgeniy
Veniaminova, Ekaterina
Costa-Nunes, João Pedro
Gorlova, Anna
Umryukhin, Aleksey
Kalueff, Allan
A.T., Proshin
Anthony, Daniel
Недорубов, Андрей Анатольевич
Chung Kwan Tse, Anna
Walitza, Susanne
Lim, Lee Wei
Lesch, Klaus-Peter
Strekalova, Tatyana
contents <p>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 (<span class="html-italic">Tph2</span>) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (<span class="html-italic">Tph2</span><sup>−/−</sup>) mice. In heterozygous male mice (<span class="html-italic">Tph2</span><sup>+/−</sup>), 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 <span class="html-italic">Tph2</span><sup>+/−</sup> mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. <span class="html-italic">Tph2</span><sup>+/−</sup> females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors <span class="html-italic">Htr1a</span> and <span class="html-italic">Htr2a</span>, glycogen synthase kinase-3 β (<span class="html-italic">GSK-3β</span>), and <span class="html-italic">c-fos</span> as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (<span class="html-italic">Mbp</span>), proteolipid protein 1 (<span class="html-italic">Plp1</span>), myelin-associated glycoprotein (<span class="html-italic">Mag</span>), and myelin oligodendrocyte glycoprotein (<span class="html-italic">Mog</span>). The expression of the plasticity markers synaptophysin (<span class="html-italic">Syp</span>) and cAMP response element binding protein (<span class="html-italic">Creb</span>), but not AMPA receptor subunit A2 (<span class="html-italic">GluA2</span>), were affected by genotype. Moreover, in a separate experiment, naïve female <span class="html-italic">Tph2</span><sup>+/−</sup> 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.</p>
format Recurso digital
id zenodo_https___doi_org_10_3390_cells11061036
institution Zenodo
language eng
publishDate 2022
publisher Zenodo
record_format zenodo
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
Veniaminova, Ekaterina
Costa-Nunes, João Pedro
Gorlova, Anna
Umryukhin, Aleksey
Kalueff, Allan
A.T., Proshin
Anthony, Daniel
Недорубов, Андрей Анатольевич
Chung Kwan Tse, Anna
Walitza, Susanne
Lim, Lee Wei
Lesch, Klaus-Peter
Strekalova, Tatyana
tryptophan hydroxylase-2 (Tph2)
female aggression
5-HT receptors
glycogen synthase kinase-3 β (GSK-3β)
myelination
predation stress
<p>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 (<span class="html-italic">Tph2</span>) results in the absence of neuronal 5-HT synthesis and excessive aggressiveness in both male and female null mutant (<span class="html-italic">Tph2</span><sup>−/−</sup>) mice. In heterozygous male mice (<span class="html-italic">Tph2</span><sup>+/−</sup>), 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 <span class="html-italic">Tph2</span><sup>+/−</sup> mice to a five-day rat predation stress paradigm and assessed their emotionality and social interaction/aggression-like behaviors. <span class="html-italic">Tph2</span><sup>+/−</sup> females exhibited excessive aggression and increased dominant behavior. Stressed mutants displayed altered gene expression of the 5-HT receptors <span class="html-italic">Htr1a</span> and <span class="html-italic">Htr2a</span>, glycogen synthase kinase-3 β (<span class="html-italic">GSK-3β</span>), and <span class="html-italic">c-fos</span> as well as myelination-related transcripts in the prefrontal cortex: myelin basic protein (<span class="html-italic">Mbp</span>), proteolipid protein 1 (<span class="html-italic">Plp1</span>), myelin-associated glycoprotein (<span class="html-italic">Mag</span>), and myelin oligodendrocyte glycoprotein (<span class="html-italic">Mog</span>). The expression of the plasticity markers synaptophysin (<span class="html-italic">Syp</span>) and cAMP response element binding protein (<span class="html-italic">Creb</span>), but not AMPA receptor subunit A2 (<span class="html-italic">GluA2</span>), were affected by genotype. Moreover, in a separate experiment, naïve female <span class="html-italic">Tph2</span><sup>+/−</sup> 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.</p>
title Predation Stress Causes Excessive Aggression in Female Mice with Partial Genetic Inactivation of Tryptophan Hydroxylase-2: Evidence for Altered Myelination-Related Processes
topic tryptophan hydroxylase-2 (Tph2)
female aggression
5-HT receptors
glycogen synthase kinase-3 β (GSK-3β)
myelination
predation stress
url https://doi.org/10.3390/cells11061036