Lafarga M, Berciano M T, Suarez I, Viadero C F, Andres M A, Berciano J
Department of Anatomy, Faculty of Medicine, University of Cantabria, Santander, Spain.
Neuroscience. 1991;40(2):337-52. doi: 10.1016/0306-4522(91)90124-7.
In order to investigate the cellular basis of human astrogliosis, we have selected the cerebellar cortex because it provides a relatively simple and geometrical organization of both neuronal and glial populations. A pathological system with severe and progressive loss of granule cells was studied: the ataxic form of Creutzfeldt-Jakob disease, where the tissue geometry is minimally disturbed. The quantitative study revealed a drastic reduction in the numerical density of granule cells in the Creutzfeldt-Jakob disease cerebellum, and a significant increase in the numerical density of astrocytes. Karyometric analysis showed that the nuclear area was significantly greater in reactive astroglial cells than in normal astroglia. Glial fibrillary acidic protein immunocytochemistry revealed astroglial hypertrophy, but the geometry and spatial domains of astroglial subtypes were strictly preserved. Vimentin expression was detected in Bergmann glia and in certain astrocytes of the granular layer. Ultrastructural analysis showed that reactive astroglia had large nuclei, with expanded interchromatinic regions which contained clusters of interchromatin granules and nuclear bodies, and prominent reticulate nucleoli. In the cytoplasm, hypertrophied bundles of intermediate filaments were observed, some of them associated with the nuclear envelope. Numerous adhering and gap junctions were also found among reactive astroglial cells. Perivascular glial processes showed a terminal web of intermediate filaments and a conspicuous plasmalemmal undercoat. Interendothelial tight junctions were preserved. Our results suggest that the severe loss of granule cells induces a highly ordered astroglial response which tends to preserve the geometry of the astroglial scaffold, the domains of each astroglial subtype, the neuronal microenvironmental conditions and the efficiency of the blood brain barrier, in order to promote neuron survival.
为了研究人类星形胶质细胞增生的细胞基础，我们选择了小脑皮质，因为它的神经元和胶质细胞群体具有相对简单且规则的组织结构。我们研究了一个颗粒细胞严重且进行性丧失的病理系统：克雅氏病的共济失调型，其组织几何结构受到的干扰最小。定量研究显示，克雅氏病小脑颗粒细胞的数值密度急剧降低，而星形胶质细胞的数值密度显著增加。核测量分析表明，反应性星形胶质细胞的核面积明显大于正常星形胶质细胞。胶质纤维酸性蛋白免疫细胞化学显示星形胶质细胞肥大，但星形胶质细胞亚型的几何形状和空间分布严格保持不变。波形蛋白表达在伯格曼胶质细胞和颗粒层的某些星形胶质细胞中被检测到。超微结构分析表明，反应性星形胶质细胞核大，染色质间区域扩大，其中含有染色质间颗粒和核体簇，以及明显的网状核仁。在细胞质中，观察到中间丝束肥大，其中一些与核膜相关。在反应性星形胶质细胞之间还发现了大量的黏附连接和缝隙连接。血管周围的胶质细胞突起显示出中间丝的终末网和明显的质膜下涂层。内皮细胞间紧密连接得以保留。我们的结果表明，颗粒细胞的严重丧失诱导了一种高度有序的星形胶质细胞反应，这种反应倾向于保留星形胶质细胞支架的几何形状、每个星形胶质细胞亚型的分布、神经元微环境条件以及血脑屏障的效率，以促进神经元存活。
