Center for Molecular and Behavioral Neuroscience, Rutgers University, Newark, New Jersey 07102, USA.
J Neurosci. 2010 Nov 10;30(45):15298-303. doi: 10.1523/JNEUROSCI.0762-10.2010.
Glucose is the primary energetic substrate of the brain, and measurements of its metabolism are the basis of major functional cerebral imaging methods. Contrary to the general view that neurons are fueled solely by glucose in proportion to their energetic needs, recent in vitro and ex vivo analyses suggest that glucose preferentially feeds astrocytes. However, the cellular fate of glucose in the intact brain has not yet been directly observed. We have used a real-time method for measuring glucose uptake in astrocytes and neurons in vivo in male rats by imaging the trafficking of the nonmetabolizable glucose analog 6-deoxy-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)-aminoglucose (6-NBDG) using two-photon microscopy. During resting conditions we found that astrocytes and neurons both take up 6-NBDG at the same rate in the barrel cortex of the rat. However, during intense neuronal activity triggered by whisker stimulation, astrocytes rapidly accelerated their uptake, whereas neuronal uptake remained almost unchanged. After the stimulation period, astrocytes returned to their preactivation rates of uptake paralleling the neuronal rate of uptake. These observations suggest that glucose is taken up primarily by astrocytes, supporting the view that functional imaging experiments based on glucose analogs extraction may predominantly reflect the metabolic activity of the astrocytic network.
葡萄糖是大脑的主要能量底物,其代谢的测量是主要功能性脑成像方法的基础。与神经元仅根据其能量需求按比例由葡萄糖提供燃料的普遍观点相反,最近的体外和离体分析表明,葡萄糖优先为星形胶质细胞提供营养。然而,完整大脑中葡萄糖的细胞命运尚未被直接观察到。我们使用了一种实时方法,通过使用双光子显微镜对不可代谢的葡萄糖类似物 6-去氧-N-(7-硝基苯并-2-恶唑-1,3-二唑-4-基)-氨基葡萄糖(6-NBDG)的转运进行成像,来测量雄性大鼠皮质桶状皮层中星形胶质细胞和神经元体内的葡萄糖摄取。在休息状态下,我们发现星形胶质细胞和神经元在大鼠的桶状皮层中以相同的速度摄取 6-NBDG。然而,在由胡须刺激引发的强烈神经元活动期间,星形胶质细胞迅速加速摄取,而神经元摄取几乎不变。在刺激期后,星形胶质细胞恢复到其预激活摄取速率,与神经元摄取速率平行。这些观察结果表明,葡萄糖主要被星形胶质细胞摄取,支持基于葡萄糖类似物提取的功能成像实验可能主要反映星形胶质细胞网络的代谢活性的观点。