Rouach Nathalie, Koulakoff Annette, Abudara Veronica, Willecke Klaus, Giaume Christian
INSERM U840, Collége de France, 11 place Marcelin Berthelot, 75005 Paris, France.
Science. 2008 Dec 5;322(5907):1551-5. doi: 10.1126/science.1164022.
Astrocytes provide metabolic substrates to neurons in an activity-dependent manner. However, the molecular mechanisms involved in this function, as well as its role in synaptic transmission, remain unclear. Here, we show that the gap-junction subunit proteins connexin 43 and 30 allow intercellular trafficking of glucose and its metabolites through astroglial networks. This trafficking is regulated by glutamatergic synaptic activity mediated by AMPA receptors. In the absence of extracellular glucose, the delivery of glucose or lactate to astrocytes sustains glutamatergic synaptic transmission and epileptiform activity only when they are connected by gap junctions. These results indicate that astroglial gap junctions provide an activity-dependent intercellular pathway for the delivery of energetic metabolites from blood vessels to distal neurons.
星形胶质细胞以活动依赖的方式为神经元提供代谢底物。然而，参与此功能的分子机制及其在突触传递中的作用仍不清楚。在这里，我们表明，缝隙连接亚基蛋白连接蛋白43和30允许葡萄糖及其代谢物通过星形胶质细胞网络进行细胞间运输。这种运输受AMPA受体介导的谷氨酸能突触活动调节。在没有细胞外葡萄糖的情况下，只有当星形胶质细胞通过缝隙连接相连时，向其输送葡萄糖或乳酸才能维持谷氨酸能突触传递和癫痫样活动。这些结果表明，星形胶质细胞缝隙连接为从血管向远端神经元输送能量代谢物提供了一条活动依赖的细胞间途径。
