Juvenile exposure to acute traumatic stress leads to long-lasting alterations in grey matter myelination in adult female but not male rats.
Juvenile exposure to acute traumatic stress leads to long-lasting alterations in grey matter myelination in adult female but not male rats.
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DOI：
10.1016/j.ynstr.2021.100319
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发表时间：
2021-05
影响因子：
5
通讯作者：
Kaufer D
中科院分区：
文献类型：
--
作者：
Breton JM;Barraza M;Hu KY;Frias SJ;Long KLP;Kaufer D
生命早期的压力会对大脑发育产生重大影响，而且越来越多的证据表明，童年时期的压力会导致以后患上精神疾病。特别是在青春期期间，对情绪调节至关重要的大脑区域，如前额叶皮层 (PFC)、杏仁核 (AMY) 和海马体 (HPC) 仍在发育，对压力高度敏感。髓磷脂水平的变化与精神疾病有关，而应激对髓磷脂和少突胶质细胞（OL）的影响正开始被探索作为精神病理学的一种新颖且未被充分认识的机制。然而，关于青春期期间急性压力对髓磷脂影响的研究很少，探索性别差异的工作就更少了。在这里，我们使用啮齿动物模型来检验以下假设：青少年时期暴露于急性创伤应激会导致边缘脑区域的 OL 和髓磷脂含量发生变化。雄性和雌性幼年大鼠在出生后第 28 天接受了 3 小时的束缚应激，并暴露在捕食者的气味中。急性应激会引起生理反应，增加皮质酮释放并减少暴露于应激的动物的体重增加。含有 PFC、AMY 和 HPC 的脑切片在青春期 (p40) 或成年期 (p95) 采集，并进行 OL 和髓磷脂标记物染色。我们发现，急性应激会在短期和长期内引起灰质 (GM) 髓鞘形成和 OL 的性别特异性变化。与相应的对照组相比，幼年时期暴露于单一应激源会增加 p40 雄性 AMY 和 HPC 中 GM 髓磷脂的含量。在 p40 时，应激暴露期间皮质酮的释放也与雄性大鼠 AMY 中的 GM 髓磷脂含量呈正相关。单一暴露于幼年应激也会导致仅对雌性大鼠产生长期影响。与对照组相比，暴露于压力的女性的所有三个大脑区域的 GM 髓磷脂含量均有所减少。急性应激暴露降低了 p40 雌性中 PFC 和 HPC OL 的密度，这可能是观察到的髓磷脂含量长期下降的原因之一。总的来说，我们的研究结果表明，青少年的大脑很容易受到短暂的严重压力源的影响。青春期期间暴露于一次短暂的创伤事件会导致雌性大鼠成年大脑中 GM 髓磷脂含量发生持久变化，而雄性大鼠则不会。这些发现强调了髓磷脂可塑性是发育关键窗口期性别特异性对扰动敏感性的潜在贡献者。第一项测试青春期急性应激对边缘灰质髓磷脂影响的研究。青少年急性应激在全球范围内降低了成年女性的髓磷脂含量。青少年急性应激会增加青春期男性的杏仁核和海马髓磷脂。
Stress early in life can have a major impact on brain development, and there is increasing evidence that childhood stress confers vulnerability for later developing psychiatric disorders. In particular, during peri-adolescence, brain regions crucial for emotional regulation, such as the prefrontal cortex (PFC), amygdala (AMY) and hippocampus (HPC), are still developing and are highly sensitive to stress. Changes in myelin levels have been implicated in mental illnesses and stress effects on myelin and oligodendrocytes (OLs) are beginning to be explored as a novel and underappreciated mechanism underlying psychopathologies. Yet there is little research on the effects of acute stress on myelin during peri-adolescence, and even less work exploring sex-differences. Here, we used a rodent model to test the hypothesis that exposure to acute traumatic stress as a juvenile would induce changes in OLs and myelin content across limbic brain regions. Male and female juvenile rats underwent 3 h of restraint stress with exposure to a predator odor on postnatal day (p) 28. Acute stress induced a physiological response, increasing corticosterone release and reducing weight gain in stress-exposed animals. Brain sections containing the PFC, AMY and HPC were taken either in adolescence (p40), or in adulthood (p95) and stained for markers of OLs and myelin. We found that acute stress induced sex-specific changes in grey matter (GM) myelination and OLs in both the short- and long-term. Exposure to a single stressor as a juvenile increased GM myelin content in the AMY and HPC in p40 males, compared to the respective control group. At p40, corticosterone release during stress exposure was also positively correlated with GM myelin content in the AMY of male rats. Single exposure to juvenile stress also led to long-term effects exclusively in female rats. Compared to controls, stress-exposed females showed reduced GM myelin content in all three brain regions. Acute stress exposure decreased PFC and HPC OL density in p40 females, perhaps contributing towards this observed long-term decrease in myelin content. Overall, our findings suggest that the juvenile brain is vulnerable to exposure to a brief severe stressor. Exposure to a single short traumatic event during peri-adolescence produces long-lasting changes in GM myelin content in the adult brain of female, but not male, rats. These findings highlight myelin plasticity as a potential contributor to sex-specific sensitivity to perturbation during a critical window of development. First study to test peri-adolescent acute stress effects on limbic grey matter myelin. Juvenile acute stress globally decreased myelin content exclusively in adult females. Juvenile acute stress increased amygdala and hippocampal myelin in adolescent males.
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