Massucci Francesco A, DiNuzzo Mauro, Giove Federico, Maraviglia Bruno, Castillo Isaac Perez, Marinari Enzo, De Martino Andrea
Dipartimento di Fisica, Sapienza Università di Roma, P,le Aldo Moro 2, 00185 Roma, Italy.
BMC Syst Biol. 2013 Oct 10;7:103. doi: 10.1186/1752-0509-7-103.
The energetics of cerebral activity critically relies on the functional and metabolic interactions between neurons and astrocytes. Important open questions include the relation between neuronal versus astrocytic energy demand, glucose uptake and intercellular lactate transfer, as well as their dependence on the level of activity.
We have developed a large-scale, constraint-based network model of the metabolic partnership between astrocytes and glutamatergic neurons that allows for a quantitative appraisal of the extent to which stoichiometry alone drives the energetics of the system. We find that the velocity of the glutamate-glutamine cycle (Vcyc) explains part of the uncoupling between glucose and oxygen utilization at increasing Vcyc levels. Thus, we are able to characterize different activation states in terms of the tissue oxygen-glucose index (OGI). Calculations show that glucose is taken up and metabolized according to cellular energy requirements, and that partitioning of the sugar between different cell types is not significantly affected by Vcyc. Furthermore, both the direction and magnitude of the lactate shuttle between neurons and astrocytes turn out to depend on the relative cell glucose uptake while being roughly independent of Vcyc.
These findings suggest that, in absence of ad hoc activity-related constraints on neuronal and astrocytic metabolism, the glutamate-glutamine cycle does not control the relative energy demand of neurons and astrocytes, and hence their glucose uptake and lactate exchange.
大脑活动的能量学关键依赖于神经元与星形胶质细胞之间的功能和代谢相互作用。重要的开放性问题包括神经元与星形胶质细胞的能量需求、葡萄糖摄取及细胞间乳酸转运之间的关系，以及它们对活动水平的依赖性。
我们构建了一个基于约束的大规模网络模型，用于描述星形胶质细胞与谷氨酸能神经元之间的代谢伙伴关系，该模型能够定量评估化学计量学单独驱动系统能量学的程度。我们发现，谷氨酸 - 谷氨酰胺循环速度（Vcyc）在Vcyc水平升高时解释了葡萄糖与氧气利用之间的部分解偶联现象。因此，我们能够根据组织氧 - 葡萄糖指数（OGI）来表征不同的激活状态。计算表明，葡萄糖根据细胞能量需求被摄取和代谢，并且糖在不同细胞类型之间的分配不受Vcyc的显著影响。此外，神经元与星形胶质细胞之间乳酸穿梭的方向和幅度取决于相对细胞葡萄糖摄取，而大致独立于Vcyc。
这些发现表明，在对神经元和星形胶质细胞代谢没有特定活动相关约束的情况下，谷氨酸 - 谷氨酰胺循环并不控制神经元和星形胶质细胞的相对能量需求，因此也不控制它们的葡萄糖摄取和乳酸交换。
