Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo
Glutamate receptor-dependent increments in lactate, glucose and oxygen metabolism evoked in rat cerebellum in vivo
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DOI：
10.1113/jphysiol.2007.144154
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发表时间：
2008-03-01
影响因子：
5.5
通讯作者：
Lauritzen, Martin
中科院分区：
文献类型：
--
作者：
Caesar, Kirsten;Hashemi, Parastoo;Lauritzen, Martin
神经元的活动与大脑的能量代谢密切相关。许多研究表明，乳酸作为神经元的能量底物与葡萄糖一样重要。据报道，乳酸产生是由谷氨酸摄取触发的，并且独立于谷氨酸受体激活。在这里，我们表明，小脑浦肯野细胞的攀爬纤维刺激增加30%的细胞外乳酸在30秒的刺激，但不是短暂的刺激期。为了探索乳酸的产生是否受突触前或突触后事件的控制，我们用CNQX沉默AMPA受体。这阻断了所有诱发的突触后活动、血流量、葡萄糖和氧气消耗的增加。CNQX也废除乳酸伴随着显着减少突触后电流的上升。乳酸的上升不受糖原磷酸化酶抑制的影响，这表明乳酸的产生是独立的糖原分解。小脑中受刺激的乳酸产生直接来源于葡萄糖摄取，并通过AMPA受体激活与神经元活动偶联。
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.