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| Format: | Recurso digital |
| Sprog: | engelsk |
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Zenodo
2022
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| Online adgang: | https://doi.org/10.3390/cells11061036 |
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| 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 |