Статья

Altered behaviour, dopamine and norepinephrine regulation in stressed mice heterozygous in TPH2 gene

T. Strekalova, E. Svirin, J. Waider, A. Gorlova, R. Cespuglio, A. Kalueff, I. Pomytkin, A. Schmitt-Boehrer, K. Lesch, D. Anthony,
2021

Gene-environment interaction (GxE) determines the vulnerability of an individual to a spectrum of stress-related neuropsychiatric disorders. Increased impulsivity, excessive aggression, and other behavioural characteristics are associated with variants within the tryptophan hydroxylase-2 (Tph2) gene, a key enzyme in brain serotonin synthesis. This phenotype is recapitulated in naïve mice with complete, but not with partial Tph2 inactivation. Tph2 haploinsufficiency in animals reflects allelic variation of Tph2 facilitating the elucidation of respective GxE mechanisms. Recently, we showed excessive aggression and altered serotonin brain metabolism in heterozygous Tph2-deficient male mice (Tph2+/−) after predator stress exposure. Here, we sought to extend these studies by investigating aggressive and anxiety-like behaviours, sociability, and the brain metabolism of dopamine and noradrenaline. Separately, Tph2+/− mice were examined for exploration activity in a novel environment and for the potentiation of helplessness in the modified swim test (ModFST). Predation stress procedure increased measures of aggression, dominancy, and suppressed sociability in Tph2+/− mice, which was the opposite of that observed in control mice. Anxiety-like behaviour was unaltered in the mutants and elevated in controls. Tph2+/− mice exposed to environmental novelty or to the ModFST exhibited increased novelty exploration and no increase in floating behaviour compared to controls, which is suggestive of resilience to stress and despair. High-performance liquid chromatography (HPLC) revealed significant genotype-dependent differences in the metabolism of dopamine, and norepinephrine within the brain tissue. In conclusion, environmentally challenged Tph2+/− mice exhibit behaviours that resemble the behaviour of non-stressed null mutants, which reveals how GxE interaction studies can unmask latent genetically determined predispositions. © 2020 The Authors

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  • 1. Version of Record от 2021-04-27

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Об авторах
  • T. Strekalova
    Department of Psychiatry and Neuropsychology, Maastricht University, Maastricht, Netherlands
  • E. Svirin
    Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
  • J. Waider
    Division of Molecular Psychiatry, Centre of Mental Health, University of Würzburg, Würzburg, Germany
  • A. Gorlova
    Neurocampus Michel Jouvet, VELIB Plateau, Claude-Bernard Lyon-1 University, Lyon, France
  • R. Cespuglio
    Laboratory of Cell and Molecular Biology and Neurobiology, Moscow Institute of Physics and Technology, Dolgoprudny, Russian Federation
  • A. Kalueff
    Institute of Translational Biomedicine, St. Petersburg State, University, St. Petersburg, Russian Federation
  • I. Pomytkin
    Ural Federal University, Ekaterinburg, Russian Federation
  • A. Schmitt-Boehrer
    Center for Advanced Cell Technologies, Institute of Regenerative Medicine, I.M. Sechenov First Moscow State Medical University, Moscow, Russian Federation
  • K. Lesch
    Department of Pharmacology, Oxford University, Oxford, United Kingdom
  • D. Anthony
Название журнала
  • Progress in Neuro-Psychopharmacology and Biological Psychiatry
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Издатель
  • Elsevier Inc.
Тип документа
  • journal article
Тип лицензии Creative Commons
  • CC
Правовой статус документа
  • Свободная лицензия
Источник
  • scopus