An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons
An increase in lactate output by brain tissue serves to meet the energy needs of glutamate-activated neurons
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DOI：
10.1523/jneurosci.19-01-00034.1999
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发表时间：
1999-01-01
影响因子：
5.3
通讯作者：
Rigor, BM
中科院分区：
文献类型：
--
作者：
Schurr, A;Miller, JJ;Rigor, BM
有氧能量代谢利用葡萄糖和氧气来产生大脑所需的所有能量。过去 13 年发表的几项研究对“激活的大脑会增加其氧化葡萄糖代谢以满足增加的能量需求”这一假设提出了挑战。提供 4 mM 葡萄糖的大鼠海马切片中的神经元功能可以耐受 5 mM 浓度的兴奋性神经递质谷氨酸 (Glu) 的激活 15 分钟，而提供 10 mM 葡萄糖的切片可以耐受 20 mM Glu 的 15 分钟激活。然而，在神经元乳酸使用受到乳酸转运蛋白抑制剂α-氰基-4-羟基肉桂酸酯 (4-ClN) 抑制的切片中，Glu 激活会导致神经元功能永久性丧失，组织乳酸含量增加两到三倍。在暴露于 Glu 期间，用葡萄糖类似物 2-脱氧-D-葡萄糖 (2DG) 抑制糖酵解会削弱大多数切片中的正常神经元功能，并显着减少激活后表现出神经元功能的切片数量。然而，当乳酸与 2DG 一起添加时，大多数切片在被 Glu 激活后具有神经元功能。 NMDA 是神经胶质谷氨酸转运蛋白的一种不可转运的谷氨酸类似物，在 4-ClN 存在的情况下给药时，不能诱导切片乳酸水平显着增加。有人认为，激活的神经元增加的能量需求是通过增加神经胶质糖酵解通量来满足的。由此形成的乳酸是一种重要的有氧能量底物，使神经元能够承受激活。
Aerobic energy metabolism uses glucose and oxygen to produce all the energy needs of the brain. Several studies published over the last 13 years challenged the assumption that the activated brain increases its oxidative glucose metabolism to meet the increased energy demands. Neuronal function in rat hippocampal slices supplied with 4 mM glucose could tolerate a 15 min activation by a 5 mM concentration of the excitatory neurotransmitter glutamate (Glu), whereas slices supplied with 10 mM glucose could tolerate a 15 min activation by 20 mM Glu. However, in slices in which neuronal lactate use was inhibited by the lactate transporter inhibitor a-cyano-4-hydroxycinnamate (4-ClN), activation by Glu elicited a permanent loss of neuronal function, with a twofold to threefold increase in tissue lactate content. Inhibition of glycolysis with the glucose analog 2-deoxy-D-glucose (2DG) during the period of exposure to Glu diminished normal neuronal function in the majority of slices and significantly reduced the number of slices that exhibited neuronal function after activation. However, when lactate was added with 2DG, the majority of the slices were neuronally functional after activation by Glu. NMDA, a nontransportable Glu analog by the glial glutamate transporter, could not induce a significant increase in slice lactate level when administered in the presence of 4-ClN. It is suggested that the heightened energy demands of activated neurons are met through increased glial glycolytic flux. The lactate thus formed is a crucial aerobic energy substrate that enables neurons to endure activation.