Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice
Region-specific myelin differences define behavioral consequences of chronic social defeat stress in mice
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DOI：
10.7554/elife.40855
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发表时间：
2019-08-13
期刊：
影响因子：
7.7
通讯作者：
Liu, Jia
中科院分区：
文献类型：
--
作者：
Bonnefil, Valentina;Dietz, Karen;Liu, Jia
暴露在压力下会增加患情绪障碍的风险。虽然一部分人表现出对压力的脆弱性，但其他人仍然保持弹性，但这些行为差异的分子基础还没有得到很好的理解。使用慢性社交失败压力模型，我们确定了表现出社交回避行为（“易感”）和逃避压力有害影响（“弹性”）的小鼠之间髓鞘形成的区域特异性差异。在所有暴露于压力的小鼠中，髓磷脂蛋白含量减少，而髓鞘厚度和节间长度减少仅在易感小鼠的内侧前额叶皮质（mPFC）中检测到，成熟少突胶质细胞较少，异染色质组蛋白标记减少。mPFC的局灶性脱髓鞘足以降低社会偏好，并在新髓鞘形成后恢复。总之，这些数据强调了mPFC髓鞘形成的功能作用，作为避免对创伤性社会经历的反应的关键决定因素。
Exposure to stress increases the risk of developing mood disorders. While a subset of individuals displays vulnerability to stress, others remain resilient, but the molecular basis for these behavioral differences is not well understood. Using a model of chronic social defeat stress, we identified region-specific differences in myelination between mice that displayed social avoidance behavior ('susceptible') and those who escaped the deleterious effect to stress ('resilient'). Myelin protein content in the nucleus accumbens was reduced in all mice exposed to stress, whereas decreased myelin thickness and internodal length were detected only in the medial prefrontal cortex (mPFC) of susceptible mice, with fewer mature oligodendrocytes and decreased heterochromatic histone marks. Focal demyelination in the mPFC was sufficient to decrease social preference, which was restored following new myelin formation. Together these data highlight the functional role of mPFC myelination as critical determinant of the avoidance response to traumatic social experiences.