Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex
Hydroxylated and non-hydroxylated sulfatide are distinctly distributed in the human cerebral cortex
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羟基化和非羟基化硫苷脂在人体大脑皮层中分布明显
DOI：
10.1016/j.neuroscience.2011.07.045
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发表时间：
2011
期刊：
影响因子：
3.3
通讯作者：
Setou M
中科院分区：
文献类型：
--
作者：
Yuki D;Sugiura Y;Zaima N;Akatsu H;Hashizume Y;Yamamoto T;Fujiwara M;Sugiyama K;Setou M
硫脂（ST）是一种鞘脂，作为髓鞘的主要成分，在中枢神经系统中具有重要作用。ST含有结构可变的神经酰胺部分，具有不同碳链长度和双键数的脂肪酸取代基。在一半的ST分子中发现脂肪酸α-2碳位置的羟基化。最近的脂肪酸2-羟化酶（FA 2 H）的遗传研究表明，这些羟基化鞘脂影响髓鞘的稳定性。但其分布情况不明。基质辅助激光解吸/电离成像质谱（MALDI-IMS）能够分析组织切片中单个ST分子种类的不同分布。我们用MALDI-IMS检查了人类大脑皮层组织切片，确定并表征了14种ST的分布。分布分析显示，在白色和灰质交界处，非羟基化和羟基化ST的组成比例明显相反，羟基化组是灰质中的优势ST种类。这些结果表明，羟基化ST在灰质中的少突胶质细胞中高度表达，并可能形成稳定的髓鞘。作为一个临床应用，我们分析了大脑阿尔茨海默病（AD）作为一个代表性的神经退行性疾病。虽然以前的AD病理学研究报告说，总ST的量减少，在大脑皮层，就组成的ST分布而言，AD大脑是类似的控制大脑。总之，我们认为MALDI-IMS是一个有用的工具，用于分析各种ST的分布，这种应用可能会提供新的见解在脱髓鞘疾病的临床研究。
Sulfatide (ST) is a sphingolipid with an important role in the central nervous system as a major component of the myelin sheath. ST contains a structurally variable ceramide moiety, with a fatty acid substituent of varying carbon-chain length and double-bond number. Hydroxylation at the α-2 carbon position of the fatty acid is found in half the population of ST molecules. Recent genetic studies of fatty acid 2-hydroxylase (FA2H) indicate that these hydroxylated sphingolipids influence myelin sheath stability. However, their distribution is unknown. Matrix-assisted laser desorption/ionization imaging mass spectrometry (MALDI-IMS) enables the analysis of distinct distributions of individual ST molecular species in tissue section. We examined human cerebral cortex tissue sections with MALDI-IMS, identifying and characterizing the distributions of 14 ST species. The distribution analysis reveals that the composition ratios of non-hydroxylated/hydroxylated STs are clearly reversed at the border between white and gray matter; the hydroxylated group is the dominant ST species in the gray matter. These results suggest that hydroxylated STs are highly expressed in oligodendrocytes in gray matter and might form stable myelin sheaths. As a clinical application, we analyzed a brain with Alzheimer's disease (AD) as a representative neurodegenerative disease. Although previous studies of AD pathology have reported that the amount of total ST is decreased in the cerebral cortex, as far as the compositional distributions of STs are concerned, AD brains were similar to those in control brains. In conclusion, we suggest that MALDI-IMS is a useful tool for analysis of the distributions of various STs and this application might provide novel insight in the clinical study of demyelinating diseases.