Department of Anatomy and Medical Imaging and Centre for Brain Research, Faculty of Medical and Health Science, University of Auckland, Private Bag 92019, Auckland, New Zealand.
Department of Anatomical Pathology, LabPlus, Auckland City Hospital, Auckland, New Zealand.
Neuroscience. 2018 Feb 21;372:289-303. doi: 10.1016/j.neuroscience.2017.12.019.
Polysialylated neural cell adhesion molecule (PSA-NCAM) is widely expressed in the adult human brain and facilitates structural remodeling of cells through steric inhibition of intercellular NCAM adhesion. We previously showed that PSA-NCAM immunoreactivity is decreased in the entorhinal cortex in Alzheimer's disease (AD). Based on available evidence, we hypothesized that a loss of PSA-NCAM interneurons may underlie this reduction. PSA-NCAM expression by interneurons has previously been described in the human medial prefrontal cortex. Here we used postmortem human brain tissue to provide further evidence of PSA-NCAM interneurons throughout the human hippocampal formation and additional cortical regions. Furthermore, PSA-NCAM cell populations were assessed in the entorhinal cortex of normal and AD cases using fluorescent double labeling and manual cell counting. We found a significant decrease in the number of PSA-NCAM cells per mm in layer II and V of the entorhinal cortex, supporting our previous description of reduced PSA-NCAM immunoreactivity. Additionally, we found a significant decrease in the proportion of PSA-NCAM cells that co-labeled with NeuN and parvalbumin, but no change in the proportion that co-labeled with calbindin or calretinin. These results demonstrate that PSA-NCAM is expressed by a variety of interneuron populations throughout the brain. Furthermore, that loss of PSA-NCAM expression by NeuN cells predominantly contributes to the reduced PSA-NCAM immunoreactivity in the AD entorhinal cortex.
多聚唾液酸化神经细胞黏附分子（PSA-NCAM）广泛表达于成人脑中，通过空间位阻抑制细胞间 NCAM 黏附，从而促进细胞结构重塑。我们之前发现，阿尔茨海默病（AD）患者的内嗅皮层中 PSA-NCAM 免疫反应性降低。基于现有证据，我们假设 PSA-NCAM 中间神经元的缺失可能是这种降低的原因。此前已经在人类前额叶皮质中描述了 PSA-NCAM 中间神经元的表达。在这里，我们使用尸检人脑组织为人类海马结构和其他皮质区域提供了 PSA-NCAM 中间神经元的进一步证据。此外，我们使用荧光双重标记和手动细胞计数评估了正常和 AD 病例的内嗅皮层中的 PSA-NCAM 细胞群体。我们发现内嗅皮层 II 层和 V 层中每平方毫米 PSA-NCAM 细胞数量显著减少，支持了我们之前描述的 PSA-NCAM 免疫反应性降低。此外，我们发现与 NeuN 和 parvalbumin 共标记的 PSA-NCAM 细胞比例显著降低，但与 calbindin 或 calretinin 共标记的细胞比例没有变化。这些结果表明，PSA-NCAM 由大脑中各种中间神经元群体表达。此外，NeuN 细胞中 PSA-NCAM 表达的丧失主要导致 AD 内嗅皮层中 PSA-NCAM 免疫反应性降低。
