Early life experiences play a vital role in contributing to healthy brain development. Adverse experiences have a lasting impact on the prefrontal cortex (PFC) and basolateral amygdala (BLA), brain regions associated with emotion regulation. Early life adversity via maternal separation (MS) has sex-specific effects on expression of parvalbumin (PV), which is expressed in fast-spiking GABAergic interneurons that are preferentially enwrapped by perineuronal nets (PNNs). Importantly, PNN formation coincides with the closure of developmental critical periods and regulates PV-expressing interneuron activity. Since aberrant PNN organization has been reported following adverse experiences in adolescent and adult rats, we investigated the impact of adversity early in life in the form of MS on the developing brain. Rat pups were separated from their dams for 4 h per day from postnatal day (P) 2-20. Tissue sections from juvenile (P20), adolescent (P40), and early adult (P70) animals containing the PFC and BLA were fluorescently stained to visualize Wisteria floribunda agglutinin+ PNNs and PV-expressing interneurons, and density and intensity was quantified. Our results confirm past reports that PFC PNNs form gradually throughout development; however, PNN density plateaus in adolescence, while intensity continues to increase into adulthood. Importantly, MS delays PNN formation in the prelimbic PFC and results in sex-specific aberrations in PNN structural integrity that do not appear until adulthood. The present findings reveal sex-, age-, and region-specific effects of early life adversity on PNN and PV maturation, implicating neuroplastic alterations following early life adversity that may be associated with sex differences in psychopathology and resilience.

中文翻译：

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母体分离对雄性和雌性大鼠神经周围神经网和表达小白蛋白的中间神经元形成的区域特异性影响。

早期生活经验对促进大脑健康发展起着至关重要的作用。不良经历会对与情绪调节相关的大脑前额叶皮层（PFC）和基底外侧杏仁核（BLA）产生持久影响。通过母体分离（MS）进行的早期生活逆境对小白蛋白（PV）的表达具有性别特异性的影响，这在快速掺入GABA的能神经元中表达，而神经元网络（PNN）优先包裹了这种神经元。重要的是，PNN的形成与发育关键时期的关闭同时发生，并调节表达PV的中间神经元的活动。由于已经报道了在青少年和成年大鼠中出现不良反应后出现异常的PNN组织的情况，因此我们以MS的形式研究了生命早期逆境对发育中的大脑的影响。从出生后第2-20天起，每天将大鼠幼崽与母鼠分开4小时。对含有PFC和BLA的幼年（P20），青春期（P40）和成年早期（P70）动物的组织切片进行荧光染色以可视化紫藤紫花凝集素+ PNN和表达PV的中间神经元，并对密度和强度进行定量。我们的结果证实了以往的报道，即PFC PNN在整个开发过程中逐渐形成。然而，PNN密度在青春期达到平稳状态，而强度持续增加直至成年。重要的是，MS会延迟前肢PFC中PNN的形成，并导致PNN结构完整性中的性别特异性畸变，直到成年才出现。本研究发现揭示了逆境对PNN和PV成熟的影响，包括性别，年龄和区域的特定影响，