Faculty of Medicine, Laboratory of Neuroendocrinology-Molecular Cell Physiology, Institute of Pathophysiology, University of Ljubljana, Zaloska 4, Ljubljana, Slovenia.
Glia. 2011 Jun;59(6):903-13. doi: 10.1002/glia.21161. Epub 2011 Mar 4.
It is becoming increasingly clear that astrocytes are no longer playing a subservient role to neurons in the central nervous system (CNS), and that these cells are being considered as active communication integrators. They respond to neurotransmitters by the regulated release of gliotransmitters. The delay between neurotransmitter activation and the release of gliotransmitters from astrocytes is in the time-domain of subseconds, much slower than the submillisecond synaptic delay. Astrocytes also control microcirculation and provide metabolic support for neurons. However, the dynamics of their energy metabolic response to neurotransmitter application is not known. We here used a FRET glucose nanosensor to dynamically measure the cytosolic glucose concentration in single astrocytes. We show that following the adrenaline or noradrenaline stimulation the availability of cytosolic glucose is increased promptly after stimulation with a time-constant of 116.7 s and 115.9 s, respectively. A decline in cytosolic glucose concentration with a time-constant of 50.7 s was observed during glutamate and 16.7 s during lactate addition to astrocytes, when these were bathed in the presence of extracellular glucose-containing solution, likely reflecting predominant glucose engagement in glycogen synthesis. In contrast, in the glucose-free extracellular solution, glutamate application to astrocytes resulted in a slow increase in cytosolic glucose concentration, consistent with the view that glutamate may be an alternative energy source in hypoglycemic conditions. We conclude that astrocytic cytosolic glucose metabolism responds in the time-domain of tens of seconds, which is slower compared to the whole brain functional magnetic resonance imaging measurements of the local intravascular hemodynamic response.
越来越明显的是，星形胶质细胞在中枢神经系统（CNS）中不再扮演神经元的从属角色，而是被认为是活跃的通讯整合器。它们通过调节神经递质的释放来响应神经递质。神经递质激活和星形胶质细胞释放神经胶质递质之间的延迟时间在亚秒域，比亚毫秒突触延迟慢得多。星形胶质细胞还控制微循环并为神经元提供代谢支持。然而，它们对神经递质应用的能量代谢反应的动力学尚不清楚。我们在这里使用 FRET 葡萄糖纳米传感器来动态测量单个星形胶质细胞中的细胞溶胶葡萄糖浓度。我们表明，在肾上腺素或去甲肾上腺素刺激后，细胞溶胶葡萄糖的可用性在刺激后迅速增加，时间常数分别为 116.7 s 和 115.9 s。在谷氨酸和乳酸添加到星形胶质细胞时，观察到细胞溶胶葡萄糖浓度以 50.7 s 的时间常数下降，当这些细胞在含有细胞外葡萄糖的溶液中孵育时，可能反映出主要的葡萄糖参与糖原合成。相比之下，在无葡萄糖的细胞外溶液中，谷氨酸应用于星形胶质细胞导致细胞溶胶葡萄糖浓度缓慢增加，这与谷氨酸可能是低血糖条件下替代能源的观点一致。我们得出结论，星形胶质细胞的细胞溶胶葡萄糖代谢在数十秒的时间域内响应，与局部血管内血流动力学响应的全脑功能磁共振成像测量相比，速度较慢。
