GLUTAMATE UPTAKE INTO ASTROCYTES STIMULATES AEROBIC GLYCOLYSIS - A MECHANISM COUPLING NEURONAL-ACTIVITY TO GLUCOSE-UTILIZATION
GLUTAMATE UPTAKE INTO ASTROCYTES STIMULATES AEROBIC GLYCOLYSIS - A MECHANISM COUPLING NEURONAL-ACTIVITY TO GLUCOSE-UTILIZATION
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DOI：
10.1073/pnas.91.22.10625
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发表时间：
1994-10-25
影响因子：
11.1
通讯作者：
MAGISTRETTI, PJ
中科院分区：
文献类型：
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作者：
PELLERIN, L;MAGISTRETTI, PJ
谷氨酸在中枢神经系统的大多数兴奋性突触中释放，通过作用于特定受体使神经元去极化。其作用通过主要经由位于神经元和星形胶质细胞两者上的Na+依赖性摄取系统从突触间隙移除而终止。在这里，我们报告说，谷氨酸，除了其受体介导的行动对神经元的兴奋性，刺激糖酵解，即，葡萄糖的利用和乳酸的产生-在星形胶质细胞中。这种代谢作用是通过激活依赖于Na F的摄取系统介导的，而不是通过与受体的相互作用。该机制涉及Na+/K+-ATP酶，其通过与谷氨酸共转运的细胞内Na+浓度的增加由生电摄取系统激活。因此，当谷氨酸从活跃的突触中释放并被星形胶质细胞吸收时，本文所述的新发现的信号通路将提供一种简单而直接的机制，将神经元活动与葡萄糖利用紧密结合。此外，谷氨酸刺激的糖酵解与脑功能成像研究获得的数据一致，表明生理激活期间局部非氧化葡萄糖利用。
Glutamate, released at a majority of excitatory synapses in the central nervous system, depolarizes neurons by acting at specific receptors. Its action is terminated by removal from the synaptic cleft mostly via Na+-dependent uptake systems located on both neurons and astrocytes. Here we report that glutamate, in addition to its receptor-mediated actions on neuronal excitability, stimulates glycolysis-i.e., glucose utilization and lactate production-in astrocytes. This metabolic action is mediated by activation of a Naf-dependent uptake system and not by interaction with receptors. The mechanism involves the Na+/K+-ATPase, which is activated by an increase in the intracellular concentration of Na+ cotransported with glutamate by the electrogenic uptake system. Thus, when glutamate is released from active synapses and taken up by astrocytes, the newly identified signaling pathway described here would provide a simple and direct mechanism to tightly couple neuronal activity to glucose utilization. In addition, glutamate-stimulated glycolysis is consistent with data obtained from functional brain imaging studies indicating local nonoxidative glucose utilization during physiological activation.