ECTOPIC DENDRITES OCCUR ONLY ON CORTICAL PYRAMIDAL CELLS CONTAINING ELEVATED GM2 GANGLIOSIDE IN ALPHA-MANNOSIDOSIS
ECTOPIC DENDRITES OCCUR ONLY ON CORTICAL PYRAMIDAL CELLS CONTAINING ELEVATED GM2 GANGLIOSIDE IN ALPHA-MANNOSIDOSIS
复制标题
DOI：
10.1073/pnas.88.24.11330
复制
发表时间：
1991-12-01
影响因子：
11.1
通讯作者：
WALKLEY, SU
中科院分区：
文献类型：
--
作者：
GOODMAN, LA;LIVINGSTON, PO;WALKLEY, SU
在多种神经元储存疾病中，皮质锥体细胞在轴突丘处产生异位树突。所有以异位树突为特征的疾病的共同特征是大脑皮质中GM 2神经节苷脂水平升高。在猫与这样的疾病，α-甘露糖苷沉积症，具有异位树突的锥体细胞的数量是小的，本研究表明，GM 2神经节苷脂存储仅在那些锥体神经元表现出异位树突。使用高尔基体电子显微镜方法与高碘酸希夫（PAS）染色，我们首先建立了锥体细胞轴承异位树突PAS+膜内含物，与糖脂的存储一致。相反，那些具有光滑轴突丘的人积累PAS-絮状包涵体，与寡糖的储存一致。接下来，应用单克隆抗体对GM 2神经节苷脂显示，亚组的锥体和内在神经元含有GM 2样免疫反应。每个GM 2+细胞含有PAS+膜内含物，表明带有异位树突的锥体细胞储存GM 2神经节苷脂。在猫与α-甘露糖苷诱导苦马豆素，一些锥体神经元表现出GM 2样免疫反应后4周的治疗，而异位树突后7周的治疗才变得明显。因此，GM 2神经节苷脂积累在锥体神经元异位树突出现的轴突丘之前。我们建议，重新启动树突生长的成熟锥体细胞所带来的积累GM 2神经节苷脂。
In a variety of neuronal storage diseases, cortical pyramidal cells elaborate ectopic dendrites at the axon hillock. A feature common to all the diseases characterized by ectopic dendrites is an elevated level of GM2 ganglioside in cerebral cortex. In cats with one such disease, alpha-mannosidosis, the number of pyramidal cells bearing ectopic dendrites is small; the present study shows that GM2 ganglioside is stored only in those pyramidal neurons exhibiting ectopic dendrites. Using a Golgi-electron microscopy method with periodic acid-Schiff (PAS) staining, we first established that pyramidal cells bearing ectopic dendrites contained PAS+ membranous inclusions, consistent with storage of glycolipids. In contrast, those with smooth axon hillocks accumulated PAS- floccular inclusions, consistent with storage of oligosaccharides. Next, application of a monoclonal antibody against GM2 ganglioside revealed that subsets of both pyramidal and intrinsic neurons contained GM2-like immunoreactivity. Every GM2+ cell contained PAS+ membranous inclusions, indicating that pyramidal cells bearing ectopic dendrites stored GM2 ganglioside. In cats with alpha-mannosidosis induced by swainsonine, some pyramidal neurons showed GM2-like immunoreactivity after 4 weeks of treatment, whereas ectopic dendrites only became evident after 7 weeks of treatment. Thus, GM2 ganglioside accumulated in pyramidal neurons before ectopic dendrites emerged from the axon hillock. We propose that the reinitiation of dendrite growth on mature pyramidal cells is brought about by accumulated GM2 ganglioside.