Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: evidence from mathematical modeling
Changes in glucose uptake rather than lactate shuttle take center stage in subserving neuroenergetics: evidence from mathematical modeling
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DOI：
10.1038/jcbfm.2009.232
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发表时间：
2010-03-01
影响因子：
6.3
通讯作者：
Giove, Federico
中科院分区：
文献类型：
--
作者：
DiNuzzo, Mauro;Mangia, Silvia;Giove, Federico
在本文中，我们结合了几个数学模型的脑代谢和营养物质的运输，以探讨在360秒的激活过程中，脑实质内的代谢物运输的能量意义。在神经元和星形胶质细胞之间均匀建模糖酵解和氧化细胞代谢，并且将刺激诱导的神经元与星形胶质细胞Na+流入设定为3：1。这些假设类似于生理条件，并得到当前文献的支持。模拟结果表明，葡萄糖扩散到小脑通过基膜占主导地位的糖提供给神经元和星形胶质细胞，而星形胶质细胞的终足转移不到4%的总葡萄糖供应给组织。即使在神经元与星形胶质细胞糖酵解（氧化）代谢的比率减半（加倍）后，以及在神经元与星形胶质细胞Na+流入减少到1：1的非生理值后，神经元对细胞旁扩散的葡萄糖的接触仍然普遍存在。值得注意的是，作为细胞间穿梭乳酸盐的置换葡萄糖当量占总脑葡萄糖摄取的6%至7%，这一量与血流中伴随的单羧酸盐排出量相当。总体而言，我们的研究结果表明，控制碳招募神经元和星形胶质细胞的葡萄糖摄取水平，而不是乳酸穿梭。Journal of Cerebral Blood Flow & Metabolism（2010）30，586-602; doi：10.1038/jcbfm.2009.232; 2009年11月4日在线发表
In this paper, we combined several mathematical models of cerebral metabolism and nutrient transport to investigate the energetic significance of metabolite trafficking within the brain parenchyma during a 360-secs activation. Glycolytic and oxidative cellular metabolism were homogeneously modeled between neurons and astrocytes, and the stimulation-induced neuronal versus astrocytic Na+ inflow was set to 3:1. These assumptions resemble physiologic conditions and are supported by current literature. Simulations showed that glucose diffusion to the interstitium through basal lamina dominates the provision of the sugar to both neurons and astrocytes, whereas astrocytic endfeet transfer less than 4% of the total glucose supplied to the tissue. Neuronal access to paracellularly diffused glucose prevails even after halving (doubling) the ratio of neuronal versus astrocytic glycolytic (oxidative) metabolism, as well as after reducing the neuronal versus astrocytic Na+ inflow to a nonphysiologic value of 1: 1. Noticeably, displaced glucose equivalents as intercellularly shuttled lactate account for similar to 6% to 7% of total brain glucose uptake, an amount comparable with the concomitant drainage of the monocarboxylate by the bloodstream. Overall, our results suggest that the control of carbon recruitment for neurons and astrocytes is exerted at the level of glucose uptake rather than that of lactate shuttle. Journal of Cerebral Blood Flow & Metabolism (2010) 30, 586-602; doi: 10.1038/jcbfm.2009.232; published online 4 November 2009