Varul Jane, Eskla Kattri-Liis, Piirsalu Maria, Innos Jürgen, Philips Mari-Anne, Visnapuu Tanel, Plaas Mario, Vasar Eero
Department of Physiology, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Center of Excellence for Genomics and Translational Medicine, Institute of Biomedicine and Translational Medicine, University of Tartu, 19 Ravila Street, 50411 Tartu, Estonia.
Brain Sci. 2021 May 29;11(6):725. doi: 10.3390/brainsci11060725.
C57BL/6NTac (Bl6) and 129S6/SvEvTac (129Sv) mice display different coping strategies in stressful conditions. Our aim was to evaluate biomarkers related to different adaptation strategies in the brain of male 129Sv and Bl6 mice. We focused on signaling pathways related to the dopamine (DA) system, N-methyl-D-aspartate (NMDA) receptor and epidermal growth factor (EGF) family, shown as the key players in behavioral adaptation. Mice from Bl6 and 129Sv lines were divided into either home cage controls (HCC group) or exposed to repeated motility testing and treated with saline for 11 days (RMT group). Distinct stress responses were reflected in severe body weight loss in 129Sv and the increased exploratory behavior in Bl6 mice. Besides that, amphetamine caused significantly stronger motor stimulation in Bl6. Together with the results from gene expression (particularly ), this study supports higher baseline activity of DA system in Bl6. Interestingly, the adaptation is reflected with opposite changes of DA markers in dorsal and ventral striatum. In forebrain, stress increased the gene expressions of and pathways more clearly in 129Sv, whereas the corresponding proteins were significantly elevated in Bl6. We suggest that not only inhibited activity of the DA system, but also reduced activity of EGF family and NMDA receptor signaling underlies higher susceptibility to stress in 129Sv. Altogether, this study underlines the better suitability of 129Sv for modelling neuropsychiatric disorders than Bl6.
C57BL/6NTac(Bl6)和129S6/SvEvTac(129Sv)小鼠在应激条件下表现出不同的应对策略。我们的目的是评估与雄性129Sv和Bl6小鼠大脑中不同适应策略相关的生物标志物。我们关注与多巴胺(DA)系统、N-甲基-D-天冬氨酸(NMDA)受体和表皮生长因子(EGF)家族相关的信号通路,这些被证明是行为适应中的关键因素。来自Bl6和129Sv品系的小鼠被分为笼内对照(HCC组)或接受重复运动测试并用生理盐水处理11天(RMT组)。不同的应激反应表现为129Sv小鼠体重严重减轻,而Bl6小鼠的探索行为增加。除此之外,苯丙胺对Bl6小鼠的运动刺激明显更强。结合基因表达结果(特别是 ),本研究支持Bl6中DA系统的基线活性更高。有趣的是,这种适应在背侧和腹侧纹状体中DA标志物的相反变化中得到体现。在前脑,应激在129Sv小鼠中更明显地增加了 和 通路的基因表达,而在Bl6小鼠中相应蛋白质显著升高。我们认为,不仅DA系统活性受到抑制,而且EGF家族和NMDA受体信号传导活性降低是129Sv小鼠对应激更高易感性的基础。总之,本研究强调129Sv比Bl6更适合用于模拟神经精神疾病。