Microglia are highly motile cells that continuously monitor the brain environment and respond to damage-associated cues. While glucose is the main energy substrate used by neurons in the brain, the nutrients metabolized by microglia to support surveillance of the parenchyma remain unexplored. Here, we use fluorescence lifetime imaging of intracellular NAD(P)H and time-lapse two-photon imaging of microglial dynamics in vivo and in situ, to show unique aspects of the microglial metabolic signature in the brain. Microglia are metabolically flexible and can rapidly adapt to consume glutamine as an alternative metabolic fuel in the absence of glucose. During insulin-induced hypoglycemia in vivo or in aglycemia in acute brain slices, glutaminolysis supports the maintenance of microglial process motility and damage-sensing functions. This metabolic shift sustains mitochondrial metabolism and requires mTOR-dependent signaling. This remarkable plasticity allows microglia to maintain their critical surveillance and phagocytic roles, even after brain neuroenergetic homeostasis is compromised.

小胶质细胞是高度活动的细胞，可连续监测大脑环境并对损伤相关提示做出反应。葡萄糖是大脑神经元使用的主要能量底物，而由小胶质细胞代谢以支持对薄壁组织进行监视的营养物质仍未开发。在这里，我们使用细胞内NAD（P）H的荧光寿命成像和体内和原位小胶质细胞动力学的延时两光子成像，以显示大脑中小胶质细胞代谢特征的独特方面。小胶质细胞具有新陈代谢的灵活性，可以在缺乏葡萄糖的情况下迅速适应消耗谷氨酰胺作为替代代谢燃料。在胰岛素诱导的体内低血糖症或急性脑切片的低血糖症期间，谷氨酰胺分解支持维持小胶质细胞的运动性和损伤感知功能。这种代谢转变维持线粒体代谢，并需要mTOR依赖性信号传导。这种显着的可塑性使小胶质细胞即使在大脑神经能量稳态失衡后仍能维持其关键的监视和吞噬作用。