Departamento de Biología Molecular, Centro de Biología Molecular Severo Ochoa, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid (CSIC-UAM), Nicolás Cabrera, 1, 28049, Madrid, Spain.
Centro de Investigación Biomédica en Red de Enfermedades Raras (CIBERER), Madrid, Spain.
Neurochem Res. 2019 Oct;44(10):2385-2391. doi: 10.1007/s11064-019-02803-7. Epub 2019 Apr 23.
The brain uses mainly glucose as fuel with an index of glucose to oxygen utilization close to 6, the maximal index if all glucose was completely oxidized. However, this high oxidative index, contrasts with the metabolic traits of the major cell types in the brain studied in culture, neurons and astrocytes, including the selective use of the malate-aspartate shuttle (MAS) in neurons and the glycerol-phosphate shuttle in astrocytes. Metabolic interactions among these cell types may partly explain the high oxidative index of the brain. In vivo, neuronal activation results in a decrease in the oxygen glucose index, which has been attributed to a stimulation of glycolysis and lactate production in astrocytes in response to glutamate uptake (astrocyte-neuron lactate shuttle, ANLS). Recent findings indicate that this is accompanied with a stimulation of pyruvate formation and astrocyte respiration, indicating that lactate formation is not the only astrocytic response to neuronal activation. ANLS proposes that neurons utilize lactate produced by neighboring astrocytes. Indeed, neurons can use lactate to support an increase in respiration with different workloads, and this depends on the Ca activation of MAS. However, whether this activation operates in the brain, particularly at high stimulation conditions, remains to be established.
大脑主要使用葡萄糖作为燃料，其葡萄糖与氧利用率的比值接近 6，这是所有葡萄糖完全氧化时的最大值。然而，这种高氧化指数与在培养中研究的大脑主要细胞类型（神经元和星形胶质细胞）的代谢特征形成鲜明对比，包括神经元中苹果酸-天冬氨酸穿梭（MAS）和星形胶质细胞中甘油磷酸穿梭的选择性使用。这些细胞类型之间的代谢相互作用可能部分解释了大脑的高氧化指数。在体内，神经元的激活会导致氧葡萄糖指数降低，这归因于星形胶质细胞对谷氨酸摄取的反应刺激了糖酵解和乳酸的产生（星形胶质细胞-神经元乳酸穿梭，ANLS）。最近的研究结果表明，这伴随着丙酮酸形成和星形胶质细胞呼吸的刺激，表明乳酸的形成不是星形胶质细胞对神经元激活的唯一反应。ANLS 提出神经元利用邻近星形胶质细胞产生的乳酸。事实上，神经元可以利用乳酸来支持在不同工作量下呼吸的增加，这取决于 MAS 的 Ca 激活。然而，这种激活是否在大脑中运作，特别是在高刺激条件下，仍有待确定。
