Anxiety disorders are prevalent mental disorders. Their predisposition involves a combination of genetic and environmental risk factors, such as psychosocial stress. Myelin plasticity was recently associated with chronic stress in several mouse models. Furthermore, we found that changes in both myelin thickness and node of Ranvier morphology after chronic social defeat stress are influenced by the genetic background of the mouse strain. To understand cellular and molecular effects of stress‐associated myelin plasticity, we established an oligodendrocyte (OL) model consisting of OL primary cell cultures isolated from the C57BL/6NCrl (B6; innately non‐anxious and mostly stress‐resilient strain) and DBA/2NCrl (D2; innately anxious and mostly stress‐susceptible strain) mice. Characterization of naïve cells revealed that D2 cultures contained more pre‐myelinating and mature OLs compared with B6 cultures. However, B6 cultures contained more proliferating oligodendrocyte progenitor cells (OPCs) than D2 cultures. Acute exposure to corticosterone, the major stress hormone in mice, reduced OPC proliferation and increased OL maturation and myelin production in D2 cultures compared with vehicle treatment, whereas only OL maturation was reduced in B6 cultures. In contrast, prolonged exposure to the synthetic glucocorticoid dexamethasone reduced OPC proliferation in both D2 and B6 cultures, but only D2 cultures displayed a reduction in OPC differentiation and myelin production. Taken together, our results reveal that genetic factors influence OL sensitivity to glucocorticoids, and this effect is dependent on the cellular maturation stage. Our model provides a novel framework for the identification of cellular and molecular mechanisms underlying stress‐associated myelin plasticity.

中文翻译：

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遗传背景调节糖皮质激素对少突胶质细胞系细胞增殖、分化和髓磷脂形成的影响

焦虑症是普遍存在的精神障碍。他们的易感性涉及遗传和环境风险因素的结合，例如社会心理压力。最近，在几种小鼠模型中，髓鞘可塑性与慢性应激有关。此外，我们发现慢性社会失败应激后髓磷脂厚度和郎飞叶形态节点的变化受到小鼠品系遗传背景的影响。为了了解应激相关髓磷脂可塑性的细胞和分子效应，我们建立了少突胶质细胞 (OL) 模型，该模型由从 C57BL/6NCrl（B6；天生非焦虑且大多具有应激弹性菌株）分离的 OL 原代细胞培养物和 DBA/ 2NCrl（D2；天生焦虑且大多对压力敏感的品系）小鼠。幼稚细胞的表征表明，与 B6 培养物相比，D2 培养物含有更多的髓鞘形成前和成熟的 OL。然而，B6 培养物比 D2 培养物含有更多的增殖少突胶质细胞祖细胞 (OPC)。与媒介物处理相比，急性暴露于小鼠主要应激激素皮质酮，在 D2 培养物中减少了 OPC 增殖并增加了 OL 成熟和髓鞘质的产生，而在 B6 培养物中仅 OL 成熟减少。相比之下，长期暴露于合成糖皮质激素地塞米松会减少 D2 和 B6 培养物中 OPC 的增殖，但只有 D2 培养物显示 OPC 分化和髓磷脂生成减少。综上所述，我们的结果表明，遗传因素影响 OL 对糖皮质激素的敏感性，并且这种影响取决于细胞成熟阶段。我们的模型为识别应激相关髓磷脂可塑性的细胞和分子机制提供了一个新的框架。