关键词: child abuse myelin parvalbumin perineuronal nets post-mortem ventromedial prefrontal cortex

Mesh : Humans Prefrontal Cortex / pathology metabolism Parvalbumins / metabolism Interneurons / pathology metabolism Male Female Adult Middle Aged Myelin Sheath / pathology metabolism Suicide Aged Autopsy Child Abuse / psychology Young Adult

来  源:   DOI:10.1093/cercor/bhae197   PDF(Pubmed)

Abstract:
Cortical parvalbumin interneurons (PV+) are major regulators of excitatory/inhibitory information processing, and their maturation is associated with the opening of developmental critical periods (CP). Recent studies reveal that cortical PV+ axons are myelinated, and that myelination along with perineuronal net (PNN) maturation around PV+ cells is associated with the closures of CP. Although PV+ interneurons are susceptible to early-life stress, their relationship between their myelination and PNN coverage remains unexplored. This study compared the fine features of PV+ interneurons in well-characterized human post-mortem ventromedial prefrontal cortex samples (n = 31) from depressed suicides with or without a history of child abuse (CA) and matched controls. In healthy controls, 81% of all sampled PV+ interneurons displayed a myelinated axon, while a subset (66%) of these cells also displayed a PNN, proposing a relationship between both attributes. Intriguingly, a 3-fold increase in the proportion of unmyelinated PV+ interneurons with a PNN was observed in CA victims, along with greater PV-immunofluorescence intensity in myelinated PV+ cells with a PNN. This study, which is the first to provide normative data on myelination and PNNs around PV+ interneurons in human neocortex, sheds further light on the cellular and molecular consequences of early-life adversity on cortical PV+ interneurons.
摘要:
皮质小清蛋白中间神经元(PV)是兴奋性/抑制性信息处理的主要调节因子,它们的成熟与发育关键时期(CP)的开启有关。最近的研究表明,皮质PV+轴突有髓鞘,髓鞘形成以及PV+细胞周围的神经周网状(PNN)成熟与CP的闭合有关。虽然PV+中间神经元容易受到早期生活压力的影响,它们的髓鞘形成和PNN覆盖率之间的关系仍未被探索.这项研究比较了在有或没有虐待儿童史(CA)的抑郁自杀和匹配对照的特征良好的人类死后腹内侧前额叶皮层样本(n=31)中PV中间神经元的优良特征。在健康的控制中,81%的所有采样PV+中间神经元显示有髓鞘轴突,虽然这些单元格的一个子集(66%)也显示了PNN,提出两个属性之间的关系。有趣的是,在CA患者中观察到无髓鞘PV中间神经元与PNN的比例增加了3倍,在具有PNN的有髓鞘PV细胞中,PV免疫荧光强度更高。这项研究,这是第一个提供关于人类新皮层PV中间神经元周围髓鞘形成和PNN的规范数据,进一步揭示了生命早期逆境对皮质PV中间神经元的细胞和分子后果。
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