Vukelić Z, Metelmann W, Müthing J, Kos M, Peter-Katalinić J
Laboratory for Biomedical Analysis, Institute for Medical Physics and Biophysics, University of Münster, Germany.
Biol Chem. 2001 Feb;382(2):259-74. doi: 10.1515/BC.2001.033.
Gangliosides from histopathologically-defined human cerebrum-resembling remnant and cerebellum from 37 and 30 gestational week-old anencephaluses were identified using mass spectrometry and high performance thin layer chromatography combined with immunochemical analysis in comparison to respective normal newborn/fetal and adult brain regions. A novel strategy of nano-electrospray ionization quadrupole time-of-flight tandem MS has been developed for identification of ganglioside components in complex mixtures. By morphoanatomical and histological investigation the anencephalic cerebral remnant was found to be aberrant, while the anencephalic cerebellum was defined as normal. Total ganglioside concentrations in the anencephalic cerebral remnant and the cerebellum were 34% and 13% lower in relation to the age-matched controls. In the cerebral remnant, GD3, GM2 and GT1b were elevated, while GD1a was decreased in the anencephalic cerebral remnant, but enriched in anencephalic cerebellum. GQ1b was reduced in both anencephalic regions. Gg4Cer, GM1b and GD1alpha, members of the alpha-series biosynthetic pathway, and neolacto-series gangliosides were found to be present in anencephalic, as well as in normal, fetal and adult brain tissues, indicating the occurrence of these biosynthetic pathways in human brain. In both cerebral and cerebellar anencephalic tissues, GM1b, GD1alpha, nLM1 and nLD1 were expressed at a higher rate in relation to normal tissue. It can be demonstrated that the anencephalic cerebral remnant, as a primitive brain structure, represents a naturally-occurring model to study the ganglioside involvement in induction of aberrant brain development.
利用质谱法、高效薄层色谱法并结合免疫化学分析，对来自37孕周和30孕周无脑儿的组织病理学定义的类似人类大脑的残余物和小脑的神经节苷脂进行了鉴定，并与相应的正常新生儿/胎儿及成人大脑区域进行了比较。已开发出一种用于鉴定复杂混合物中神经节苷脂成分的新型纳米电喷雾电离四极杆飞行时间串联质谱策略。通过形态解剖学和组织学研究发现，无脑儿的大脑残余物异常，而无脑儿的小脑被定义为正常。与年龄匹配的对照组相比，无脑儿大脑残余物和小脑中的总神经节苷脂浓度分别降低了34%和13%。在大脑残余物中，GD3、GM2和GT1b升高，而GD1a在无脑儿大脑残余物中降低，但在无脑儿小脑中富集。GQ1b在两个无脑儿区域均减少。发现α-系列生物合成途径的成员Gg4Cer、GM1b和GD1α以及新乳糖系列神经节苷脂存在于无脑儿以及正常胎儿和成人脑组织中，表明这些生物合成途径在人类大脑中存在。在无脑儿的大脑和小脑组织中，GM1b、GD1α、nLM1和nLD1相对于正常组织的表达率更高。可以证明，无脑儿大脑残余物作为一种原始脑结构，是研究神经节苷脂参与异常脑发育诱导的天然模型。
