Glutamine is an essential cerebral metabolite. Several critical brain processes are directly linked to glutamine, including ammonia homeostasis, energy metabolism and neurotransmitter recycling. Astrocytes synthesize and release large quantities of glutamine, which is taken up by neurons to replenish the glutamate and GABA neurotransmitter pools. Astrocyte glutamine hereby sustains the glutamate/GABA-glutamine cycle, synaptic transmission and general brain function. Cerebral glutamine homeostasis is linked to the metabolic coupling of neurons and astrocytes, and relies on multiple cellular processes, including TCA cycle function, synaptic transmission and neurotransmitter uptake. Dysregulations of processes related to glutamine homeostasis are associated with several neurological diseases and may mediate excitotoxicity and neurodegeneration. In particular, diminished astrocyte glutamine synthesis is a common neuropathological component, depriving neurons of an essential metabolic substrate and precursor for neurotransmitter synthesis, hereby leading to synaptic dysfunction. While astrocyte glutamine synthesis is quantitatively dominant in the brain, oligodendrocyte-derived glutamine may serve important functions in white matter structures. In this review, the crucial roles of glial glutamine homeostasis in the healthy and diseased brain are discussed. First, we provide an overview of cellular recycling, transport, synthesis and metabolism of glutamine in the brain. These cellular aspects are subsequently discussed in relation to pathological glutamine homeostasis of hepatic encephalopathy, epilepsy, Alzheimer’s disease, Huntington’s disease and amyotrophic lateral sclerosis. Further studies on the multifaceted roles of cerebral glutamine will not only increase our understanding of the metabolic collaboration between brain cells, but may also aid to reveal much needed therapeutic targets of several neurological pathologies.

谷氨酰胺是一种必需的脑代谢产物。几个关键的大脑过程与谷氨酰胺直接相关，包括氨稳态、能量代谢和神经递质循环。星形胶质细胞合成并释放大量谷氨酰胺，神经元吸收谷氨酰胺以补充谷氨酸和 GABA 神经递质库。星形胶质细胞谷氨酰胺由此维持谷氨酸/GABA-谷氨酰胺循环、突触传递和一般脑功能。脑谷氨酰胺稳态与神经元和星形胶质细胞的代谢耦合有关，并依赖于多种细胞过程，包括 TCA 循环功能、突触传递和神经递质摄取。与谷氨酰胺稳态相关的过程失调与多种神经系统疾病有关，并可能介导兴奋性毒性和神经变性。特别是，星形胶质细胞谷氨酰胺合成减少是一种常见的神经病理学成分，剥夺了神经元必需的代谢底物和神经递质合成的前体，从而导致突触功能障碍。虽然星形胶质细胞谷氨酰胺合成在大脑中占主导地位，但少突胶质细胞衍生的谷氨酰胺可能在白质结构中发挥重要作用。在这篇综述中，讨论了神经胶质谷氨酰胺稳态在健康和患病大脑中的关键作用。首先，我们概述了大脑中谷氨酰胺的细胞循环、运输、合成和代谢。随后将讨论这些细胞方面与肝性脑病、癫痫、阿尔茨海默病、亨廷顿舞蹈病和肌萎缩侧索硬化的病理性谷氨酰胺稳态相关的问题。