Central Institute of Engineering, Electronics and Analytics, ZEA-3, Forschungszentrum Jülich, Jülich, Germany.
Cécile and Oskar Vogt Institute of Brain Research, Medical Faculty, Heinrich Heine University Düsseldorf, Düsseldorf, Germany.
Brain Struct Funct. 2018 Jul;223(6):2767-2783. doi: 10.1007/s00429-018-1660-y. Epub 2018 Apr 10.
The primary visual cortex (area V1) is an extensively studied part of the cerebral cortex with well-characterized connectivity, cellular and molecular architecture and functions (for recent reviews see Amunts and Zilles, Neuron 88:1086-1107, 2015; Casagrande and Xu, Parallel visual pathways: a comparative perspective. The visual neurosciences, MIT Press, Cambridge, pp 494-506, 2004). In humans, V1 is defined by heavily myelinated fibers arriving from the radiatio optica that form the Gennari stripe in cortical layer IV, which is further subdivided into laminae IVa, IVb, IVcα and IVcβ. Due to this unique laminar pattern, V1 represents an excellent region to test whether multimodal mass spectrometric imaging could reveal novel biomolecular markers for a functionally relevant parcellation of the human cerebral cortex. Here we analyzed histological sections of three post-mortem brains with matrix-assisted laser desorption/ionization mass spectrometry imaging and laser ablation inductively coupled plasma mass spectrometry imaging to investigate the distribution of lipids, proteins and metals in human V1. We identified 71 peptides of 13 different proteins by in situ tandem mass spectrometry, of which 5 proteins show a differential laminar distribution pattern revealing the border between V1 and V2. High-accuracy mass measurements identified 123 lipid species, including glycerolipids, glycerophospholipids and sphingolipids, of which at least 20 showed differential distribution within V1 and V2. Specific lipids labeled not only myelinated layer IVb, but also IVa and especially IVc in a layer-specific manner, but also and clearly separated V1 from V2. Elemental imaging further showed a specific accumulation of copper in layer IV. In conclusion, multimodal mass spectrometry imaging identified novel biomolecular and elemental markers with specific laminar and inter-areal differences. We conclude that mass spectrometry imaging provides a promising new approach toward multimodal, molecule-based cortical parcellation.
初级视皮层（V1 区）是大脑皮层中研究得非常透彻的一部分，其连接、细胞和分子结构以及功能都已得到很好的描述（最近的综述见 Amunts 和 Zilles, Neuron 88:1086-1107, 2015; Casagrande 和 Xu, Parallel visual pathways: a comparative perspective. The visual neurosciences, MIT Press, Cambridge, pp 494-506, 2004）。在人类中，V1 区由来自视放射的大量髓鞘纤维定义，这些纤维在皮质 IV 层形成杰纳利条纹（Gennari stripe），IV 层进一步细分为 IVa、IVb、IVcα 和 IVcβ 层。由于这种独特的分层模式，V1 区是一个极好的区域，可以测试多模态质谱成像是否可以揭示用于人类大脑皮层功能相关分区的新型生物分子标志物。在这里，我们使用基质辅助激光解吸/电离质谱成像和激光烧蚀电感耦合等离子体质谱成像分析了三个死后大脑的组织切片，以研究脂质、蛋白质和金属在人类 V1 区的分布。我们通过原位串联质谱鉴定了 71 种肽，来自 13 种不同的蛋白质，其中 5 种蛋白质显示出分层分布模式的差异，揭示了 V1 和 V2 之间的边界。高精度质量测量鉴定了 123 种脂质，包括甘油磷脂、甘油磷酸脂和神经酰胺，其中至少 20 种在 V1 和 V2 内显示出不同的分布。特定的脂质不仅标记了有髓鞘的 IVb 层，而且还以分层特异性的方式标记了 IVa 层，特别是 IVc 层，并且还清晰地将 V1 与 V2 分开。元素成像进一步显示了 IV 层中铜的特定积累。总之，多模态质谱成像确定了具有特定分层和区域间差异的新型生物分子和元素标志物。我们得出结论，质谱成像为基于分子的多模态皮质分区提供了一种很有前途的新方法。
