Duarte João M N, Girault Freya-Merret, Gruetter Rolf
Laboratory for Functional and Metabolic Imaging, École Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.
Department of Radiology, University of Lausanne, Lausanne, Switzerland.
J Neurosci Res. 2015 Jul;93(7):1009-18. doi: 10.1002/jnr.23531. Epub 2014 Dec 17.
The brain uses lactate produced by glycolysis as an energy source. How lactate originated from the blood stream is used to fuel brain metabolism is not clear. The current study measures brain metabolic fluxes and estimates the amount of pyruvate that becomes labeled in glial and neuronal compartments upon infusion of [3-(13)C]lactate. For that, labeling incorporation into carbons of glutamate and glutamine was measured by (13)C magnetic resonance spectroscopy at 14.1 T and analyzed with a two-compartment model of brain metabolism to estimate rates of mitochondrial oxidation, glial pyruvate carboxylation, and the glutamate-glutamine cycle as well as pyruvate fractional enrichments. Extracerebral lactate at supraphysiological levels contributes at least two-fold more to replenish the neuronal than the glial pyruvate pools. The rates of mitochondrial oxidation in neurons and glia, pyruvate carboxylase, and glutamate-glutamine cycles were similar to those estimated by administration of (13)C-enriched glucose, the main fuel of brain energy metabolism. These results are in agreement with primary utilization of exogenous lactate in neurons rather than astrocytes.
大脑将糖酵解产生的乳酸用作能量来源。目前尚不清楚源自血流的乳酸如何为大脑代谢提供能量。当前的研究测量了大脑的代谢通量，并估计了在注入[3-(13)C]乳酸后，神经胶质细胞和神经元区室中被标记的丙酮酸的量。为此，通过在14.1 T下的(13)C磁共振波谱法测量了谷氨酸和谷氨酰胺碳中的标记掺入情况，并使用大脑代谢的双区室模型进行分析，以估计线粒体氧化、神经胶质丙酮酸羧化以及谷氨酸-谷氨酰胺循环的速率以及丙酮酸的分数富集情况。超生理水平的脑外乳酸对神经元丙酮酸池的补充作用至少比对神经胶质细胞的补充作用大两倍。神经元和神经胶质细胞中的线粒体氧化速率、丙酮酸羧化酶以及谷氨酸-谷氨酰胺循环与通过给予富含(13)C的葡萄糖（大脑能量代谢的主要燃料）所估计的速率相似。这些结果与神经元而非星形胶质细胞对外源乳酸的优先利用相一致。
