Department of Neuroscience, Physiology and Pharmacology, University College London, London WC1E 6BT, United Kingdom.
J Neurosci. 2012 Jun 27;32(26):8940-51. doi: 10.1523/JNEUROSCI.0026-12.2012.
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 (reduced nicotinamide adenine dinucleotide), 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.
神经活动被认为最初通过糖酵解而不是氧化磷酸化来触发 ATP 的产生，原因有三：糖酵解酶与离子泵有关；神经元可以通过激活星形胶质细胞中的糖酵解来产生乳酸，从而增加能量供应；活动增加葡萄糖摄取量的程度超过 O₂摄取量。在大鼠海马切片中，即使使用乳酸脱氢酶阻断物阻止乳酸生成，或者仅用 20%的超氧合 O₂模拟生理 O₂水平，神经元活动也会迅速降低细胞外 O₂和细胞内 NADH（还原型烟酰胺腺嘌呤二核苷酸）的水平。药理学分析显示，能量预算中，11%的 O₂用于突触前动作电位，17%用于突触前 Ca²⁺内流和递质释放，46%用于突触后谷氨酸受体，26%用于突触后动作电位，与理论大脑能量预算大致相符。因此，介导大脑信息处理的主要机制最初都是由氧化磷酸化提供能量的，而星形胶质细胞-神经元乳酸穿梭并不需要发生这种情况。
