Zwingmann Claudia, Leibfritz Dieter
Department of Organic Chemistry, University of Bremen, Leobener Strasse, NW2-C, 28359 Bremen, Germany.
NMR Biomed. 2003 Oct-Nov;16(6-7):370-99. doi: 10.1002/nbm.850.
Glial metabolism and their metabolic trafficking with neurons are essential parts of neuronal function, as they modulate, by this means, neuronal activity. Ex vivo and in vitro (13)C-NMR spectroscopy have been used to monitor neural cellular and tissue metabolism. Special emphasis has been given to the metabolic specialization of astrocytes and its enzymatic regulation. For this purpose primary cell cultures are useful tools to study neuronal-glial metabolic relationships as the extracellular fluid can be investigated and manipulated by various stimuli. In astrocytes, glucose is utilized predominantly anaerobically. Glycolysis is interrelated to the astrocytic TCA cycle via bi-directional signals and metabolic exchange processes between astrocytes and neurons. Besides glucose oxidation, neuronally released glutamate is metabolized through the glial TCA cycle. The flexibility of glutamate metabolism, depending on ammonia and energy homeostasis, and the discovered pyruvate recycling pathway in astrocytes, modulates the glutamine-glutamate cycle. (13)C-NMR studies have extended the concept of the "non-stoichiometric" glutamate-glutamine cycle between neurons and astrocytes. An alanine-lactate shuttle between neurons and astrocytes contributes to nitrogen transfer from neurons to astrocytes, recycles energy substrates for neurons, and in return promotes intercellular glutamine-glutamate cycling. The conversion of alanine to lactate in astrocytes is regulated by intracytosolic pyruvate compartmentation. In essence, the metabolic flexibility and compartmentalized enzymatic specialization of astrocytes buffers the brain tissue against metabolic impairments and excitotoxicity in response to extracellular stimuli, some of them being released by neurons. These in vitro studies using (13)C-NMR spectroscopy provide important knowledge regarding physiological and pathophysiological regulation of neural metabolism to improve our understanding of general brain function.
神经胶质细胞的代谢及其与神经元的代谢物质交换是神经元功能的重要组成部分，因为它们通过这种方式调节神经元活动。体外和体内的¹³C-核磁共振波谱已被用于监测神经细胞和组织的代谢。研究特别强调了星形胶质细胞的代谢特化及其酶促调节。为此，原代细胞培养是研究神经元-神经胶质细胞代谢关系的有用工具，因为细胞外液可以通过各种刺激进行研究和操纵。在星形胶质细胞中，葡萄糖主要通过无氧代谢被利用。糖酵解通过星形胶质细胞与神经元之间的双向信号和代谢交换过程与星形胶质细胞的三羧酸循环相互关联。除了葡萄糖氧化外，神经元释放的谷氨酸通过神经胶质细胞的三羧酸循环进行代谢。谷氨酸代谢的灵活性取决于氨和能量稳态，以及在星形胶质细胞中发现的丙酮酸循环途径，调节谷氨酰胺-谷氨酸循环。¹³C-核磁共振研究扩展了神经元和星形胶质细胞之间“非化学计量”谷氨酸-谷氨酰胺循环的概念。神经元和星形胶质细胞之间的丙氨酸-乳酸穿梭有助于氮从神经元转移到星形胶质细胞，为神经元回收能量底物，反过来促进细胞间谷氨酰胺-谷氨酸循环。星形胶质细胞中丙氨酸向乳酸的转化受胞质内丙酮酸分隔的调节。本质上，星形胶质细胞的代谢灵活性和区室化酶促特化可缓冲脑组织免受细胞外刺激（其中一些由神经元释放）引起的代谢损伤和兴奋性毒性。这些使用¹³C-核磁共振波谱的体外研究提供了有关神经代谢生理和病理生理调节的重要知识，以增进我们对大脑一般功能的理解。
