Astrocytes as the glucose shunt for glutamatergic neurons at high activity: an in silico study.
Astrocytes as the glucose shunt for glutamatergic neurons at high activity: an in silico study.
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星形胶质细胞作为高活性谷氨酸能神经元的葡萄糖分流：一项计算机研究。
DOI：
10.1152/jn.90377.2008
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发表时间：
2009
影响因子：
2.5
通讯作者：
Calvetti,Daniela
中科院分区：
文献类型：
--
作者：
Occhipinti,Rossana;Somersalo,Erkki;Calvetti,Daniela
在高神经活性下的谷氨酸能神经元的优选底物的问题已经被激烈地争论了十多年，因为葡萄糖的首要地位的经典假说（CH）已经被星形胶质细胞-神经元乳酸穿梭假说（ANLSH）挑战，该假说用星形胶质细胞产生的乳酸代替葡萄糖的首要地位。我们进行贝叶斯通量平衡分析（BFBA）与细胞脑能量学的一个新的数学模型，包括详细的生化途径和星形胶质细胞和神经元之间的每种细胞类型的细胞质和线粒体的分区。在我们的计算机模拟研究结果的支持下，与先前发表的结果非常一致，我们证实了葡萄糖分流假说（GSH），即在高活性期间，神经元中磷酸果糖激酶（PFK）酶的抑制损害神经元糖酵解，使星形胶质细胞流出的乳酸被谷氨酸能神经元吸收的过程成为可能，而在低活性时，葡萄糖仍然是神经元的优选底物。我们推测，ANLS是一个分流利用的神经元绕过他们的糖酵解受损的抑制PFK与增加氧化磷酸化在高神经元活性。
The question of the preferred substrate of glutamatergic neurons at high neural activity has been vibrantly debated for over a decade since the classical hypothesis (CH) of the primacy of glucose has been challenged by the astrocyte-neuron lactate shuttle hypothesis (ANLSH), which replaces the primacy of glucose with astrocyte produced lactate. We perform Bayesian Flux Balance Analysis (BFBA) with a new mathematical model of cellular brain energetics, comprising detailed biochemical pathways in and between astrocytes and glutamatergic neurons and partitioning of each cell type into cytosol and mitochondria. Supported by the results of our in silico studies, which are in remarkable agreement with previously published results, we posit the Glucose Shunt Hypothesis (GSH) that during high activity, the inhibition of the phosphofructokinase (PFK) enzyme in neuron impairs neuronal glycolysis, enabling the process by which lactate effluxed by astrocytes is taken up by glutamatergic neurons, whereas at low activity, glucose remains the preferred substrate for neurons. We postulate that the ANLS is a shunt utilized by glutamatergic neurons to bypass their glycolysis impaired by the inhibition of PFK in connection with increased oxidative phosphorylation at high neuronal activity.