Abstract：
Perineuronal nets (PNNs) are a type of extracellular matrix (ECM) that play a significant role in synaptic activity and plasticity of interneurons in health and disease. We researched PNNs\' regional and laminar representation and molecular composition using immunohistochemistry and transcriptome analysis of Brodmann areas (BA) 9, 14r, and 24 in 25 human postmortem brains aged 13-82 years. The numbers of VCAN- and NCAN-expressing PNNs, relative to the total number of neurons, were highest in cortical layers I and VI while WFA-binding (WFA+) PNNs were most abundant in layers III-V. The ECM glycosylation pattern was the most pronounced regional difference, shown by a significantly lower proportion of WFA+ PNNs in BA24 (3.27 ± 0.69%) compared to BA9 (6.32 ± 1.73%; P = 0.0449) and BA14 (5.64 ± 0.71%; P = 0.0278). The transcriptome of late developmental and mature stages revealed a relatively stable expression of PNN-related transcripts (log2-transformed expression values: 6.5-8.5 for VCAN and 8.0-9.5 for NCAN). Finally, we propose a classification of PNNs that envelop GABAergic neurons in the human cortex. The significant differences in PNNs\' morphology, distribution, and molecular composition strongly suggest an involvement of PNNs in specifying distinct microcircuits in particular cortical regions and layers.
摘要：
神经周网（PNN）是一种细胞外基质（ECM），在健康和疾病中在突触活动和中间神经元的可塑性中起重要作用。我们使用免疫组织化学和Brodmann区域（BA）9，14r的转录组分析研究了PNN的区域和层状表示和分子组成，25个13-82岁的人类死后大脑中有24个。表达VCAN和NCAN的PNN的数量，相对于神经元的总数，在皮质层I和VI中最高，而WFA结合（WFA）PNN在III-V层中最丰富。ECM糖基化模式是最明显的区域差异，BA24中WFA+PNN的比例(3.27±0.69%)显著低于BA9(6.32±1.73%;P=0.0449)和BA14(5.64±0.71%;P=0.0278)。发育后期和成熟阶段的转录组显示PNN相关转录本的相对稳定表达（log2转化的表达值：VCAN为6.5-8.5，NCAN为8.0-9.5）。最后,我们提出了在人类皮层中包裹GABA能神经元的PNN的分类。PNN形态的显著差异，分布，和分子组成强烈表明PNN参与指定特定皮质区域和层中的不同微电路。
