Research output: Contribution to journal › Article › peer-review
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; Umriukhin, Aleksei; Kalueff, Allan V.; Proshin, Andrey; Anthony, Daniel; Nedorubov, Andrey; Tse, Anna Chung Kwan; Walitza, Susanne; Lim, Lee Wei; Lesch, Klaus Peter; Strekalova, Tatyana.
In: Cells, Vol. 11, No. 6, 1036, 18.03.2022.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - Predation Stress Causes Excessive Aggression in Female Mice with Partial Genetic Inactivation of Tryptophan Hydroxylase-2
T2 - Evidence for Altered Myelination-Related Processes
AU - Svirin, Evgeniy
AU - Veniaminova, Ekaterina
AU - Costa-Nunes, João Pedro
AU - Gorlova, Anna
AU - Umriukhin, Aleksei
AU - Kalueff, Allan V.
AU - Proshin, Andrey
AU - Anthony, Daniel
AU - Nedorubov, Andrey
AU - Tse, Anna Chung Kwan
AU - Walitza, Susanne
AU - Lim, Lee Wei
AU - Lesch, Klaus Peter
AU - Strekalova, Tatyana
N1 - Publisher Copyright: © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
PY - 2022/3/18
Y1 - 2022/3/18
N2 - 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.
AB - 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.
KW - 5-HT receptors
KW - Female aggression
KW - Glycogen synthase kinase-3 β (GSK-3β)
KW - Myelination
KW - Predation stress
KW - Tryptophan hydroxylase-2 (Tph2)
KW - Predatory Behavior
KW - Rats
KW - Glycogen Synthase Kinase 3 beta
KW - Male
KW - Tryptophan Hydroxylase/genetics
KW - Animals
KW - Serotonin/metabolism
KW - Female
KW - Aggression/physiology
KW - Mice
UR - http://www.scopus.com/inward/record.url?scp=85126589605&partnerID=8YFLogxK
UR - https://www.mendeley.com/catalogue/b796a737-a03f-3e18-9aa1-34c452bf2449/
U2 - 10.3390/cells11061036
DO - 10.3390/cells11061036
M3 - Article
C2 - 35326487
AN - SCOPUS:85126589605
VL - 11
JO - Cells
JF - Cells
SN - 2073-4409
IS - 6
M1 - 1036
ER -
ID: 95284723