Child abuse (CA) is a major risk factor for depression, and strongly associates with suicidal behavior during adulthood. Neuroimaging studies have reported widespread changes in white matter integrity and brain connectivity in subjects with a history of CA. Although such observations could reflect changes in myelin and oligodendrocyte function, their cellular underpinnings have never been addressed. Using postmortem brain samples from depressed suicides with or without history of CA and matched controls (18 per group), we aimed to characterize the effects of CA on oligodendrocyte-lineage (OL) cells in the ventromedial prefrontal white matter. Using immunoblotting, double-labeling immunofluorescence and stereological estimates of stage-specific markers, we found that CA is associated with increased numbers of mature myelinating oligodendrocytes, accompanied by decreased numbers of more immature OL cells. This was paralleled by an increased expression of transcription factor MASH1, which is involved in the terminal differentiation of the OL, suggesting that CA may trigger an increased maturation, or bias the populations of OL cells toward a more mature phenotype. Some of these effects, which were absent in the brain of depressed suicides with no history of CA, were also found to recover with age, suggesting that changes in the balance of the OL may reflect a transient adaptive mechanism triggered by early-life adversity. In conclusion, our results indicate that CA in depressed suicides is associated with an imbalance of the OL in the ventromedial prefrontal white matter, an effect that could lead to myelin remodeling and long-term connectivity changes within the limbic network.

中文翻译：

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虐待儿童与腹侧前额叶白质中少突胶质细胞系细胞的失衡有关。

虐待儿童（CA）是抑郁症的主要危险因素，并与成年期间的自杀行为密切相关。神经影像学研究已报道患有CA病史的受试者白质完整性和大脑连接性发生了广泛变化。尽管这些观察结果可以反映髓鞘和少突胶质细胞功能的变化，但它们的细胞基础从未得到解决。我们使用来自有或没有CA病史的抑郁自杀者的死后脑样本以及匹配的对照（每组18个），我们旨在表征CA对腹侧前额叶白质中少突胶质细胞谱系（OL）细胞的影响。使用免疫印迹，双标记免疫荧光和特定阶段标记的立体估计，我们发现CA与成熟的髓鞘少突胶质细胞数量增加有关，伴随着更多的未成熟OL细胞数量减少。与此平行的是，转录因子MASH1的表达增加，这与OL的终末分化有关，这表明CA可能触发成熟度增加，或使OL细胞群体偏向更成熟的表型。在没有CA历史的抑郁型自杀者的大脑中，这些作用中的某些现象也随着年龄的增长而恢复，这表明OL平衡的变化可能反映了早期逆境触发的短暂适应机制。总之，我们的结果表明，抑郁型自杀中的CA与腹侧前额叶白质中OL的失衡有关，这种作用可能导致髓鞘重塑和边缘网络内的长期连通性改变。