Department of Neurology, Mail Slot 500, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR, 72205, USA.
Department of Cell Biology and Physiology, University of New Mexico School of Medicine, Albuquerque, NM, 87131, USA.
Neurochem Res. 2020 Nov;45(11):2607-2630. doi: 10.1007/s11064-020-03125-9. Epub 2020 Sep 18.
Accurate quantification of cellular contributions to rates of substrate utilization in resting, activated, and diseased brain is essential for interpretation of data from studies using [F]fluorodeoxyglucose-positron-emission tomography (FDG-PET) and [C]glucose/magnetic resonance spectroscopy (MRS). A generally-accepted dogma is that neurons have the highest energy demands of all brain cells, and calculated neuronal rates of glucose oxidation in awake, resting brain accounts for 70-80%, with astrocytes 20-30%. However, these proportions do not take cell type volume fractions into account. To evaluate the conclusion that neuron-astrocyte glucose oxidation rates are similar when adjusted for astrocytic volume fraction (Hertz, Magn Reson Imaging 2011; 29, 1319), the present study analyzed data from 31 studies. On average, astrocytes occupy 6.1, 9.6, and 15% of tissue volume in hippocampus, cerebral cortex, and cerebellum, respectively, and regional astrocytic metabolic rates are adjusted for volume fraction by multiplying by 17.6, 11.4, and 6.8, respectively. After adjustment, astrocytic glucose oxidation rates in resting awake rat brain are 4-10 fold higher than neuronal oxidation rates. Volume-fraction adjustment also increases brain glycogen concentrations and utilization rates to be similar to or exceed exercising muscle. Ion flux calculations to evaluate sodium/potassium homeostasis during neurotransmission are not correct if astrocyte-neuron volume fractions are assumed to be equal. High rates of glucose and glycogen utilization after adjustment for volume fraction indicate that astrocytic energy demands are much greater than recognized, with most of the ATP being used for functions other than glutamate processing in the glutamate-glutamine cycle, challenging the notion that astrocytes 'feed hungry neurons'.
准确量化细胞对静息、激活和患病大脑中底物利用速率的贡献，对于解释使用 [F]氟脱氧葡萄糖正电子发射断层扫描（FDG-PET）和 [C]葡萄糖/磁共振波谱（MRS）进行的研究数据至关重要。一个普遍接受的观点是，神经元是所有脑细胞中能量需求最高的，在清醒、静息状态下计算出的神经元葡萄糖氧化率占 70-80%，而星形胶质细胞占 20-30%。然而，这些比例并没有考虑细胞类型的体积分数。为了评估神经元-星形胶质细胞葡萄糖氧化率在调整星形胶质细胞体积分数后相似的结论（Hertz，Magn Reson Imaging 2011；29，1319），本研究分析了 31 项研究的数据。平均而言，星形胶质细胞分别占据海马体、大脑皮层和小脑组织体积的 6.1%、9.6%和 15%，并且区域星形胶质细胞代谢率通过乘以 17.6、11.4 和 6.8 分别进行体积分数调整。调整后，静息清醒大鼠大脑中星形胶质细胞的葡萄糖氧化率比神经元氧化率高 4-10 倍。体积分数调整还会增加脑糖原浓度和利用率，使其与运动肌肉相似或超过运动肌肉。如果假设星形胶质细胞-神经元体积分数相等，那么评估神经递质传递过程中钠/钾离子平衡的离子通量计算将是不正确的。调整体积分数后葡萄糖和糖原利用率的增加表明，星形胶质细胞的能量需求比人们所认识的要大得多，大部分 ATP 用于谷氨酸-谷氨酰胺循环中谷氨酸处理以外的功能，这挑战了星形胶质细胞“喂养饥饿神经元”的观点。
