Caesar Kirsten, Hashemi Parastoo, Douhou Aicha, Bonvento Gilles, Boutelle Martyn G, Walls Anne B, Lauritzen Martin
Department of Neuroscience and Pharmacology, University of Copenhagen, Copenhagen, Denmark.
J Physiol. 2008 Mar 1;586(5):1337-49. doi: 10.1113/jphysiol.2007.144154. Epub 2008 Jan 10.
Neuronal activity is tightly coupled with brain energy metabolism. Numerous studies have suggested that lactate is equally important as an energy substrate for neurons as glucose. Lactate production is reportedly triggered by glutamate uptake, and independent of glutamate receptor activation. Here we show that climbing fibre stimulation of cerebellar Purkinje cells increased extracellular lactate by 30% within 30 s of stimulation, but not for briefer stimulation periods. To explore whether lactate production was controlled by pre- or postsynaptic events we silenced AMPA receptors with CNQX. This blocked all evoked rises in postsynaptic activity, blood flow, and glucose and oxygen consumption. CNQX also abolished rises in lactate concomitantly with marked reduction in postsynaptic currents. Rises in lactate were unaffected by inhibition of glycogen phosphorylase, suggesting that lactate production was independent of glycogen breakdown. Stimulated lactate production in cerebellum is derived directly from glucose uptake, and coupled to neuronal activity via AMPA receptor activation.
神经元活动与脑能量代谢紧密相关。大量研究表明，乳酸作为神经元的能量底物与葡萄糖同等重要。据报道，乳酸的产生由谷氨酸摄取触发，且与谷氨酸受体激活无关。在此我们表明，对小脑浦肯野细胞的攀缘纤维刺激在刺激后30秒内使细胞外乳酸增加了30%，但较短刺激时间则无此现象。为探究乳酸的产生是受突触前还是突触后事件控制，我们用CNQX使AMPA受体失活。这阻断了所有诱发的突触后活动、血流以及葡萄糖和氧气消耗的增加。CNQX还消除了乳酸的增加，同时突触后电流显著减少。糖原磷酸化酶的抑制并未影响乳酸的增加，这表明乳酸的产生与糖原分解无关。小脑受刺激时产生的乳酸直接来源于葡萄糖摄取，并通过AMPA受体激活与神经元活动相关联。
