Glial role in neuronal development and function

Bergmann glia(BG)是一种单极小脑星形胶质细胞，与移行颗粒细胞(GC)和成熟的浦肯野细胞(PC)相关。利用定位于星形胶质细胞/星形胶质细胞系质膜上的谷氨酸转运体GLAST的细胞化学优势，分析了BG的形态分化。胚胎第13天(El3)仅在脑室带有GLAST mRNA的表达。在胚胎14d，它们首先出现在外套层，在那里它们有椭圆形到拉长的细胞体和到达软膜表面的放射状纤维，这表明小脑径向胶质细胞的迁移。从E18到P7，皮质中表达GLAST的细胞形成了BG的特征(即PC小体周围单层排列，Bergmann纤维中表达胶质纤维酸性蛋白)，并进一步上调GLAST的表达，而其他小脑区域的GLAST表达则转变为多极星形胶质细胞，并下调其表达。从P7到P21，Bergmann纤维均发生了…变化从线状到网状结构呈深到浅的梯度，浅层线形部分与PC树突生长的尖端紧密接触，而较深的网状部分反映了膜状突起的活跃形成，它们精心地侵入神经纤维包围PC突触。因此，在完成单极皮质星形胶质细胞后，BG的Bergmann纤维在活跃的突触发生阶段进行动态转换，导致PC突触的结构成熟。与树突尖端的密切接触进一步表明，Bergmann纤维可能是PC树突树枝和迁移GC的结构底物。为了进一步探索分子基础，我们通过产生丝氨酸合成酶3-磷酸甘油脱氢酶(3PGDH)的抗体来研究神经元-神经胶质细胞与丝氨酸代谢的关系。3PGDH在星形胶质细胞和嗅鞘胶质细胞发育过程中均有选择性的高表达。在发育中的小脑中，3PGDH阴性的PC树突起的生长尖端与3PGDH阳性的Bergmann纤维相接触。这些结果表明，BG生物合成丝氨酸并供应给PC是树突和神经胶质纤维在发育过程中结构紧密联系的可能原因之一。较少

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