Child abuse (CA) is a strong predictor of psychopathologies and suicide, altering normal trajectories of brain development in areas closely linked to emotional responses such as the prefrontal cortex (PFC). Yet, the cellular underpinnings of these enduring effects are unclear. Childhood and adolescence are marked by the protracted formation of perineuronal nets (PNNs), which orchestrate the closure of developmental windows of cortical plasticity by regulating the functional integration of parvalbumin interneurons (PV) into neuronal circuits. Using well-characterized post-mortem brain samples, we show that a history of CA is specifically associated with increased densities and morphological complexity of WFL-labeled PNNs in the ventromedial PFC (BA11/12), possibly suggesting increased recruitment and maturation of PNNs. Through single-nucleus sequencing and fluorescent in-situ hybridization, we found that the expression of canonical components of PNNs is enriched in oligodendrocyte progenitor cells (OPCs), and that they are upregulated in CA victims. These correlational findings suggest that early-life adversity may lead to persistent patterns of maladaptive behaviors by reducing the neuroplasticity of cortical circuits through the enhancement of developmental OPC-mediated PNN formation.

中文翻译：

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虐待儿童与腹内侧前额叶皮层神经周围网的增加有关：少突胶质祖细胞的可能含义

虐待儿童 (CA) 是精神病态和自杀的强预测因子，会改变与情绪反应密切相关的区域的大脑发育正常轨迹，例如前额叶皮层 (PFC)。然而，这些持久影响的细胞基础尚不清楚。童年和青春期的标志是神经周围网络 (PNN) 的长期形成，它通过调节小白蛋白中间神经元 (PV) 与神经元回路的功能整合来协调皮质可塑性发育窗口的关闭。使用特征明确的死后大脑样本，我们表明 CA 的历史与腹内侧 PFC (BA11/12) 中 WFL 标记的 PNN 的密度和形态复杂性的增加特别相关，这可能表明 PNN 的募集和成熟增加。通过单核测序和荧光原位杂交，我们发现少突胶质祖细胞 (OPCs) 中 PNN 经典成分的表达丰富，并且它们在 CA 受害者中上调。这些相关发现表明，早期生活中的逆境可能通过增强发育性 OPC 介导的 PNN 形成来降低皮质回路的神经可塑性，从而导致持续的适应不良行为模式。