Sphingosylphosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type B
Sphingosylphosphorylcholine in Niemann-Pick disease brain: Accumulation in type A but not in type B
复制标题
DOI：
10.1023/a:1022501702403
复制
发表时间：
1999-02-01
影响因子：
4.4
通讯作者：
Vanier, MT
中科院分区：
文献类型：
--
作者：
Rodriguez-Lafrasse, C;Vanier, MT
一项针对神经元病性尼曼-匹克病鞘磷脂酶缺陷型患者脑脂质的研究表明，鞘磷脂异常积聚仅发生在神经病性 A 型患者的大脑中，而非神经元病性 B 型患者的大脑中。A 型脑中还存在其他脂质异常。相比之下，B 型患者的脑脂质谱正常。由于溶血鞘脂与其他遗传性溶酶体鞘脂沉积症的生化发病机制有关，因此使用 HPLC 方法和荧光检测邻苯二醛衍生物，专门研究了脑和神经外组织中鞘氨醇磷酰胆碱（溶血鞘磷脂）的出现。在正常和病理对照中观察到接近或低于检测限（10 pmol/mg 组织蛋白）的水平。在两名 Niemann-Pick A 型患者的大脑中观察到了显着的积累（在患有严重和轻度神经病程的 27 个月和 16 个月大的儿童中分别为 830 和 430 pmol/mg 蛋白质），而这种积累在疾病的胎儿阶段并不存在。一名3.5岁B型患者的脑组织未发现明显增加。在肝脏和脾脏中，两种类型的疾病中都观察到异常高的鞘氨醇磷酸胆碱水平，并表明在发育过程中逐渐增加。这项研究确定了 B 型尼曼-匹克病脑组织的完整性，并表明溶血化合物鞘氨醇磷酸胆碱可能在 A 型神经病性脑功能障碍的病理生理学中发挥作用。
A study of brain lipids in patients with the sphingomyelinase-deficient types of Niemann-Pick disease demonstrated that abnormal accumulation of sphingomyelin occurs only in the brain of neuronopathic type A patients but not in the non-neuronopathic type B. Additional lipid abnormalities were present in the type A brain. In contrast, the brain lipid profile was normal in type B patients. Since lysosphingolipids have been implicated in the biochemical pathogenesis of other genetic lysosomal sphingolipidoses, the occurrence of sphingosylphosphorylcholine (lysosphingomyelin) was specifically investigated in brain and extraneural tissues, using an HPLC method with fluorescent detection of orthophtalaldehyde derivatives. Levels close to or below the limit of detection (10 pmol/mg tissue protein) were observed in normal and pathological controls. A striking accumulation was observed in brain of two Niemann-Pick type A patients (830 and 430 pmol/mg protein in 27-and 16-month-old children with severe and milder neurological course, respectively), which was not present at the fetal stage of the disease. No significant increase was found in brain tissue from a 3.5 year-old type B patient. In liver and spleen, abnormally high sphingosylphosphorylcholine levels were observed in both types of the disease, with indication of a progressive increase during development. This study establishes the integrity of brain tissue in Niemann-Pick disease type B and suggests that the lysocompound sphingosylphosphorylcholine could play a role in the pathophysiology of brain dysfunction in the neuronopathic type A.