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| Autori principali: | , , , , , , , , , , , , , |
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| Natura: | Recurso digital |
| Lingua: | inglese |
| Pubblicazione: |
Zenodo
2022
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| Soggetti: | |
| Accesso online: | https://doi.org/10.3390/cells11061036 |
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Sommario:
- <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>