Gryksa Katharina, Schäfer Theresa, Gareis Franziska, Fuchs Elena, Royer Melanie, Schmidtner Anna K, Bludau Anna, Neumann Inga D
Department of Behavioral and Molecular Neurobiology, University of Regensburg, Regensburg, Germany.
Front Neurosci. 2024 Dec 9;18:1493619. doi: 10.3389/fnins.2024.1493619. eCollection 2024.
The development of stress-related psychopathologies, often associated with socio-emotional dysfunctions, is crucially determined by genetic and environmental factors, which shape the individual vulnerability or resilience to stress. Especially early adolescence is considered a vulnerable time for the development of psychopathologies. Various mouse strains are known to age-dependently differ in social, emotional, and endocrine stress responses based on genetic and epigenetic differences. This highlights the importance of the qualified selection of an adequate strain and age for any biomedical research. Neuropeptides like oxytocin (OXT) can contribute to individual and strain-dependent differences in emotional and social behaviors.
In this study, we compared anxiety- and fear-related, as well as social behavior and pain perception between male adolescent and adult mice of two commonly used strains, C57BL/6N (BL6) and CD1.
We revealed BL6 mice as being more anxious, less social, and more susceptible toward non-social and social trauma, both in adolescence and adulthood. Furthermore, during development from adolescence toward adulthood, BL6 mice lack the reduction in fear- and anxiety-related behavior seen in adult CD1 mice and show even higher social fear-responses and perception of noxious stimuli during adulthood. Analysis of the OXT system, by means of receptor autoradiography and immunohistochemistry, showed strain- and age-specific differences in OXT receptor (OXTR) binding in relevant brain regions, but no differences in the number of hypothalamic OXT neurons. However, intracerebroventricular infusion of OXT did neither reduce the high level of anxiety-related nor of social fear-related behavior in adult BL6 mice.
In summary, we show that male BL6 mice present an anxious and stress vulnerable phenotype in adolescence, which further exacerbates in adulthood, whereas CD1 mice show a more resilient socio-emotional state both in adolescence as well as during adulthood. These consistent behavioral differences between the two strains might only be partly mediated by differences in the OXT system but highlight the influence of early-life environment on socio-emotional behavior.
与压力相关的精神病理学的发展，通常与社会情感功能障碍相关，其关键取决于遗传和环境因素，这些因素塑造了个体对压力的易感性或恢复力。特别是青春期早期被认为是精神病理学发展的脆弱时期。已知各种小鼠品系基于遗传和表观遗传差异，在社会、情感和内分泌应激反应方面存在年龄依赖性差异。这凸显了为任何生物医学研究合理选择合适品系和年龄的重要性。像催产素（OXT）这样的神经肽可导致个体和品系依赖性的情绪和社会行为差异。
在本研究中，我们比较了两种常用品系C57BL/6N（BL6）和CD1的雄性青春期和成年小鼠在焦虑和恐惧相关方面，以及社会行为和疼痛感知。
我们发现BL6小鼠在青春期和成年期都更焦虑、社交性更低，并且对非社交和社交创伤更敏感。此外，在从青春期向成年期的发育过程中，BL6小鼠缺乏成年CD1小鼠中所见的恐惧和焦虑相关行为的减少，并且在成年期表现出更高的社会恐惧反应和对有害刺激的感知。通过受体放射自显影和免疫组织化学对OXT系统的分析表明，相关脑区中OXT受体（OXTR）结合存在品系和年龄特异性差异，但下丘脑OXT神经元数量没有差异。然而，脑室内注入OXT既没有降低成年BL6小鼠的高焦虑相关行为水平，也没有降低其社会恐惧相关行为水平。
总之，我们表明雄性BL6小鼠在青春期呈现出焦虑和应激易感性表型，在成年期会进一步加剧，而CD1小鼠在青春期以及成年期都表现出更具恢复力的社会情感状态。这两个品系之间这些一致的行为差异可能仅部分由OXT系统的差异介导，但凸显了早期生活环境对社会情感行为的影响。
