Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing.
Oxidative phosphorylation, not glycolysis, powers presynaptic and postsynaptic mechanisms underlying brain information processing.
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DOI：
10.1523/jneurosci.0026-12.2012
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发表时间：
2012-06-27
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影响因子：
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通讯作者：
Attwell D
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作者：
Hall CN;Klein-Flügge MC;Howarth C;Attwell D
神经活动最初被认为是通过糖酵解而不是氧化磷酸化来触发ATP的产生，原因有三：糖酵解酶与离子泵相关；神经元可能通过激活星形胶质细胞中的糖酵解来产生乳酸来增加能量供应；活动增加葡萄糖摄取而不是O2摄取。在大鼠海马片上，神经元活动迅速降低细胞外O2和细胞内NADH水平，甚至在乳酸脱氢酶被阻断以阻止乳酸产生的情况下，或者仅用20%的超融合O2来模拟生理O2水平。药理学分析表明，能量平衡中，11%的氧气消耗在突触前动作电位上，17%在突触前钙进入和递质释放上，46%在突触后谷氨酸受体上，26%在突触后动作电位上，与理论上的脑能量收支基本一致。因此，调节大脑信息处理的主要机制最初都是由氧化磷酸化提供动力的，而这并不需要星形胶质细胞-神经元乳酸穿梭来实现。
Neural activity has been suggested to initially trigger ATP production by glycolysis, rather than oxidative phosphorylation, for three reasons: glycolytic enzymes are associated with ion pumps; neurons may increase their energy supply by activating glycolysis in astrocytes to generate lactate; and activity increases glucose uptake more than O2 uptake. In rat hippocampal slices neuronal activity rapidly decreased the levels of extracellular O2 and intracellular NADH, even with lactate dehydrogenase blocked to prevent lactate generation, or with only 20% superfused O2 to mimic physiological O2 levels. Pharmacological analysis revealed an energy budget in which 11% of O2 use was on presynaptic action potentials, 17% was on presynaptic Ca2+ entry and transmitter release, 46% was on postsynaptic glutamate receptors and 26% was on postsynaptic action potentials, in approximate accord with theoretical brain energy budgets. Thus, the major mechanisms mediating brain information processing are all initially powered by oxidative phosphorylation, and an astrocyte-neuron lactate shuttle is not needed for this to occur.