Glial role in neuronal development and function

伯格曼胶质细胞（BG）是与迁移颗粒细胞（GCs）和成熟浦肯野细胞（PCs）相关的单极小脑星形胶质细胞。利用定位于突状胶质/星形胶质细胞系质膜上的谷氨酸转运蛋白GLAST的细胞化学优势，我们分析了BG的形态分化。在胚胎第13天（El3），表达GLAST mRNA的细胞仅存在于心室区。E14时，它们首先出现在地幔区，胞体呈椭圆形至细长状，径向纤维到达脑顶表面，提示小脑径向胶质细胞迁移。从E18到P7，皮层表达GLAST的细胞建立了BG的特征（即PC体周围单层排列和伯格曼纤维胶质原纤维酸性蛋白的表达），并进一步上调了GLAST的表达，而其他小脑区域的GLAST则转变为多极星形胶质细胞并下调了表达。从P7到P21，伯格曼纤维呈线性到网状的渐变变化；浅层线状部分与PC树突的生长尖端紧密接触，而较深的网状部分反映了膜状突起的活跃形成，这些膜状突起精心侵入神经细胞，包围PC突触。因此，在成为单极皮质星形胶质细胞后，BG的伯格曼纤维在突触形成活跃期发生动态转化，导致PC突触结构成熟。与树突尖端的密切接触进一步表明，伯格曼纤维可能是树突化PC和迁移gc的结构基质。为了进一步探究丝氨酸代谢的分子基础，我们通过产生针对丝氨酸合成酶3-磷酸甘油脱氢酶（3PGDH）的抗体，研究了丝氨酸代谢过程中神经元与神经胶质的关系。3PGDH在星形胶质细胞和嗅鞘胶质细胞的发育过程中高度选择性表达。在小脑发育中，3pgdh阴性的PC树突生长尖端与3pgdh阳性的伯格曼纤维接触。这些结果表明，BG的丝氨酸生物合成及其向PCs的供应是树突和胶质纤维在发育过程中密切结构关系的合理原因之一。少

The Bergmann glia (BG) is unipolar cerebellar astrocytes associating with migrating granule cells (GCs) and mature Purkinje cells (PCs). By taking cytochemical advantage of glutamate transporter GLAST localized on the plasmalemma of raidal glia/astrocyte lineage, we analyzed the morphodifferentiation of BG. Cells expressing GLAST mRNA were present only in the ventricular zone at embryonic day 13 (El3). At E14, they first appeared in the mantle zone, where they had oval to elongated cell bodies and radial fibers reaching the pial surface, suggesting the migration of cerebellar radial glia. From E18 to P7, GLAST-expressing cells in the cortex established characteristics of BG (i.e., monolayer alignment around PC bodies and expression of glial fibrillary acidic protein in Bergmann fibers) and further up-regulated GLAST expression, whereas those in other cerebellar regions were changed into multipolar astrocytes and down-regulated the expression. From P7 to P21, Bergmann fibers were change … More d from linear to reticular form in a deep-to-superficial gradient; the superficial linear portion was intimately contacted with the growing tips of PC dendrites, while the deeper reticular portion reflected active formation of membranous protrusions invading the neuropil elaborately to surround PC synapses. Following the accomplishment as unipolar cortical astrocytes, therefore, Bergmann fibers of BG undergo dynamic transformation in the active synaptogenic phase, leading to structural maturation of PC synapses. Intimate contacts with dendritic tips further suggest that Bergmann fibers could be a structural substrate for arborizing PC dendrites as well as for migrating GCs.To further pursue the molecular basis, neuron-glial relationship on serine metabolism was examined by producing antibody to serine synthetic enzyme 3-phosphoglycerate dehydrogenase (3PGDH). 3PGDH was highly and selectively expressed throughout development in astrocytes and olfactory ensheathing glia. In the cerebellum, the growing tips of 3PGDH-negative PC dendrites were contacted to 3PGDH-positive Bergmann fibers in developing cerebellum. These results suggest that serine biosynthesis by BG and its supply to PCs are one of the plausible reason for the intimate structural relationships between dendrites and glial fibers during development. Less