Predation Stress Causes Excessive Aggression in Female Mice with Partial Genetic Inactivation of Tryptophan Hydroxylase-2: Evidence for Altered Myelination-Related Processes
| Autor: | Evgeniy Svirin, Ekaterina Veniaminova, João Pedro Costa-Nunes, Anna Gorlova, Aleksei Umriukhin, Allan V. Kalueff, Andrey Proshin, Daniel C. Anthony, Andrey Nedorubov, Anna Chung Kwan Tse, Susanne Walitza, Lee Wei Lim, Klaus-Peter Lesch, Tatyana Strekalova |
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| Přispěvatelé: | Psychiatrie & Neuropsychologie, RS: MHeNs - R3 - Neuroscience, Repositório da Universidade de Lisboa, University of Zurich, Lim, Lee Wei, Strekalova, Tatyana |
| Jazyk: | angličtina |
| Předmět: |
Male
INDUCED ANHEDONIA PROTEIN EXPRESSION REAL TIME POLYMERASE CHAIN REACTION 2700 General Medicine PROTEIN C FOS Tryptophan Hydroxylase MOUSE ANIMAL EXPERIMENT Serotonin/metabolism EXPERIMENTAL BEHAVIORAL TEST Mice SOCIAL INTERACTION FORCED SWIM TEST APPETITE PHYSIOLOGICAL STRESS MUTATION GENETIC TRANSCRIPTION glycogen synthase kinase-3 beta (GSK-3 beta) SEROTONIN myelination General Medicine MOUSE MODEL 10058 Department of Child and Adolescent Psychiatry female aggression FEMALE Aggression RECEPTOR GENE TRYPTOPHAN HYDROXYLASE 2 AGGRESSION PREDATORY BEHAVIOR HT receptors Tryptophan Hydroxylase/genetics PREDATION STRESS TREADMILL EXERCISE RNA EXTRACTION SWIMMING LOSS OF FUNCTION MUTATION AGONISTIC BEHAVIOR predation stress FOOD COMPETITION TEST PROTEOLIPID PROTEIN NONHUMAN tryptophan hydroxylase-2 (Tph2) 5-HT receptors glycogen synthase kinase-3 β (GSK-3β) CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN EMOTIONALITY Glycogen Synthase Kinase 3 beta SYNAPTOPHYSIN BEHAVIOR CHANGE FOOD INTAKE ANIMALS MYELIN BASIC PROTEIN MAJOR DEPRESSION ANIMAL AGGRESSIVENESS Predatory Behavior RAT MYELINATION HOME CAGE ASSAY PREFRONTAL CORTEX ANIMAL MODEL HIPPOCAMPAL NEUROGENESIS HTR1A GENE C57BL/6 MICE SOCIAL DEFEAT GLYCOGEN SYNTHASE KINASE-3 Β (GSK-3Β) SEROTONINERGIC SYSTEM TRYPTOPHAN HYDROXYLASE-2 (TPH2) TRANSCRIPTION FACTOR ELEVATED ZERO MAZE TEST Glycogen synthase kinase-3 β (GSK-3β) PREDATION AMPA RECEPTOR MOLECULAR MARKER 3β) MYELIN ASSOCIATED GLYCOPROTEIN INDUCED AGGRESSION TEST REAL TIME REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION LIGHT-DARK TEST OLIGODENDROGLIA WILD TYPE MOUSE COMPLEMENTARY DNA GENE INACTIVATION GLYCOGEN SYNTHASE KINASE 3BETA Female BRAIN PROTEIN GENE EXPRESSION GENETICS EXPLORATORY BEHAVIOR TEST GLYCOGEN SYNTHASE KINASE 3 BETA Aggression/physiology 3 β (GSK 610 Medicine & health METABOLISM glycogen synthase kinase RATS TRYPTOPHAN HYDROXYLASE ANIMAL TISSUE NERVE CELL PLASTICITY MYELIN OLIGODENDROCYTE GLYCOPROTEIN OPEN FIELD TEST Animals ddc:610 ARTICLE 2 (Tph2) GENE EXPRESSION PROFILING PHYSIOLOGY MALE GLYCERALDEHYDE 3 PHOSPHATE DEHYDROGENASE (NADP) Rats CONTROLLED STUDY TRANSCRIPTION FACTOR-1 MYT1 MICE FEMALE AGGRESSION HTR2A GENE MATERNAL SEPARATION 5-HT RECEPTORS PENTOBARBITAL |
| Zdroj: | Cells, 11(6):1036. Multidisciplinary Digital Publishing Institute (MDPI) Cells; Volume 11; Issue 6; Pages: 1036 Cells |
| ISSN: | 2073-4409 |
| DOI: | 10.3390/cells11061036 |
| Popis: | © 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.). |
| Databáze: | OpenAIRE |
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