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Glial role in neuronal development and function

胶质细胞在神经元发育和功能中的作用

基本信息

批准号：
10214201
负责人：
WATANABE Masahiko
金额：
$ 18.37万
依托单位：
Hokkaido University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research on Priority Areas (B)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

项目摘要

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

Bergmann胶质细胞（BG）是小脑的单极星形胶质细胞，与迁移颗粒细胞（GC）和成熟的浦肯野细胞（PC）相关。利用谷氨酸转运体GLAST定位于星形胶质细胞/星形胶质细胞系质膜的细胞化学优势，我们分析了BG的形态分化。表达GLAST mRNA的细胞仅存在于胚胎第13天（E13）的脑室区。在E14，它们首先出现在外套带，在那里它们具有椭圆形至细长的细胞体和到达软膜表面的放射状纤维，这表明小脑放射状胶质细胞的迁移。从E18到P7，皮质中表达GLAST的细胞建立了BG的特征（即，PC体周围的单层排列和Bergmann纤维中胶质细胞酸性蛋白的表达）并进一步上调GLAST的表达，而小脑其他区域的星形胶质细胞则转变为多极星形胶质细胞并下调其表达。从P7到P21，Bergmann纤维改变 ...更多信息结果表明，PC树突的生长呈从深到浅的梯度变化，浅的线状部分与PC树突的生长尖端紧密接触，而深的网状部分则反映了膜突起的活跃形成，膜突起侵入神经元并包围PC突触。因此，在作为单极皮质星形胶质细胞完成后，BG的Bergmann纤维在活跃的突触发生阶段经历动态转化，导致PC突触的结构成熟。与树突尖端的亲密接触进一步表明，Bergmann纤维可能是一个结构基板的arborizing PC树突以及迁移GCs.To进一步追求的分子基础，神经胶质细胞的丝氨酸代谢的关系进行了研究，通过生产抗体丝氨酸合成酶3-磷酸甘油酸脱氢酶（3 PGDH）。3 PGDH在星形胶质细胞和嗅鞘胶质细胞的整个发育过程中高度选择性表达。在小脑中，3 PGDH阴性PC树突的生长尖端与发育中小脑的3 PGDH阳性Bergmann纤维接触。这些结果表明，丝氨酸生物合成BG和其供应PC的树突和神经胶质纤维之间的密切结构关系在发展过程中的一个合理的原因。少