Glycogen serves as an energy source that maintains astrocyte cell proliferation in the neonatal telencephalon
Glycogen serves as an energy source that maintains astrocyte cell proliferation in the neonatal telencephalon
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DOI：
10.1177/0271678x16665380
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发表时间：
2017-06-01
影响因子：
6.3
通讯作者：
Ono, Katsuhiko
中科院分区：
文献类型：
--
作者：
Gotoh, Hitoshi;Nomura, Tadashi;Ono, Katsuhiko
当细胞进行细胞增殖和分化以促进哺乳动物神经元发育时，需要大量的能量。早期的新生小鼠面临短暂的饥饿，并利用储存的能量来生存或支持发育。糖原是一种由葡萄糖形成的支链多糖，可作为星形胶质细胞的能量储存来满足快速的能量需求。尽管糖原存在于放射状胶质细胞和星形胶质细胞中，但糖原在发育过程中的作用仍不清楚。在本研究中，我们证明糖原在脑室下区和吻侧迁移流的谷氨酸天冬氨酸转运蛋白（GLAST）+星形胶质细胞中积累。由于糖原磷酸化酶（糖原代谢的必需酶）的增加，出生后糖原水平显着下降。在原代培养物和体内，糖原磷酸化酶的抑制减少了星形胶质细胞的增殖。 G1 期细胞数量的增加与细胞周期蛋白依赖性激酶抑制剂的上调或视网膜母细胞瘤蛋白 (pRB) 磷酸化的下调相结合，而 pRB 是细胞周期进展的决定因素。这些结果表明，糖原在产前阶段在位于特定区域的星形胶质细胞中积累，并用作产后早期维持正常发育的能量来源。
Large amounts of energy are required when cells undergo cell proliferation and differentiation for mammalian neuronal development. Early neonatal mice face transient starvation and use stored energy for survival or to support development. Glycogen is a branched polysaccharide that is formed by glucose, and serves as an astrocytic energy store for rapid energy requirements. Although it is present in radial glial cells and astrocytes, the role of glycogen during development remains unclear. In the present study, we demonstrated that glycogen accumulated in glutamate aspartate transporter (GLAST)+ astrocytes in the subventricular zone and rostral migratory stream. Glycogen levels markedly decreased after birth due to the increase of glycogen phosphorylase, an essential enzyme for glycogen metabolism. In primary cultures and invivo, the inhibition of glycogen phosphorylase decreased the proliferation of astrocytic cells. The number of cells in the G1 phase increased in combination with the up-regulation of cyclin-dependent kinase inhibitors or down-regulation of the phosphorylation of retinoblastoma protein (pRB), a determinant for cell cycle progression. These results suggest that glycogen accumulates in astrocytes located in specific areas during the prenatal stage and is used as an energy source to maintain normal development in the early postnatal stage.