McGill Group for Suicide Studies, Douglas Mental Health University Institute, McGill University, 6875 Blvd LaSalle, H4H 1R3, Montreal, QC, Canada.
Integrated Program in Neuroscience, McGill University, 1033 Av des Pins Ouest, H3A 1A1, Montreal, QC, Canada.
Glycobiology. 2024 Jun 22;34(8). doi: 10.1093/glycob/cwae049.
Perineuronal nets (PNNs) are a condensed subtype of extracellular matrix that form a net-like coverings around certain neurons in the brain. PNNs are primarily composed of chondroitin sulfate (CS) proteoglycans from the lectican family that consist of CS-glycosaminoglycan side chains attached to a core protein. CS disaccharides can exist in various isoforms with different sulfation patterns. Literature suggests that CS disaccharide sulfation patterns can influence the function of PNNs as well as their labeling. This study was conducted to characterize such interregional CS disaccharide sulfation pattern differences in adult human (n = 81) and mouse (n = 19) brains. Liquid chromatography tandem mass spectrometry was used to quantify five different CS disaccharide sulfation patterns, which were then compared to immunolabeling of PNNs using Wisteria Floribunda Lectin (WFL) to identify CS-glycosaminoglycans and anti-aggrecan to identify CS proteoglycans. In healthy brains, significant regional and species-specific differences in CS disaccharide sulfation and single versus double-labeling pattern were identified. A secondary analysis to investigate how early-life stress impacts these PNN features discovered that although early-life stress increases WFL+ PNN density, the CS-glycosaminoglycan sulfation code and single versus double PNN-labeling distributions remained unaffected in both species. These results underscore PNN complexity in traditional research, emphasizing the need to consider their heterogeneity in future experiments.
周围神经毡（PNNs）是一种浓缩的细胞外基质亚型，在大脑中的某些神经元周围形成网状覆盖物。PNNs 主要由粘蛋白家族的软骨素硫酸盐（CS）蛋白聚糖组成，其由与核心蛋白相连的 CS-糖胺聚糖侧链组成。CS 二糖可以以不同的硫酸化模式存在于各种异构体中。文献表明，CS 二糖硫酸化模式可以影响 PNN 的功能及其标记。本研究旨在表征成年人类（n=81）和小鼠（n=19）大脑中的区域性 CS 二糖硫酸化模式差异。采用液相色谱串联质谱法对 5 种不同的 CS 二糖硫酸化模式进行定量，并与 PNN 用 Wisteria Floribunda Lectin（WFL）标记（以识别 CS-糖胺聚糖）和抗 aggrecan 标记（以识别 CS 蛋白聚糖）进行比较。在健康的大脑中，发现 CS 二糖硫酸化和单-双标记模式存在明显的区域和物种特异性差异。一项关于早期生活应激如何影响这些 PNN 特征的二次分析发现，尽管早期生活应激增加了 WFL+PNN 密度，但在两种物种中，CS-糖胺聚糖硫酸化模式和单-双 PNN 标记分布保持不变。这些结果突出了 PNN 在传统研究中的复杂性，强调了在未来实验中需要考虑其异质性。
