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Reevaluation of Astrocyte-Neuron Energy Metabolism with Astrocyte Volume Fraction Correction: Impact on Cellular Glucose Oxidation Rates, Glutamate-Glutamine Cycle Energetics, Glycogen Levels and Utilization Rates vs. Exercising Muscle, and Na+/K+ Pumping Rates.
Neurochemical Research ( IF 3.7 ) Pub Date : 2020-09-18 , DOI: 10.1007/s11064-020-03125-9
Gerald A Dienel 1, 2 , Douglas L Rothman 3
Affiliation  

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 [18F]fluorodeoxyglucose-positron-emission tomography (FDG-PET) and [13C]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'.



中文翻译:

通过星形胶质细胞体积分数校正重新评估星形胶质细胞-神经元能量代谢:对细胞葡萄糖氧化率、谷氨酸-谷氨酰胺循环能量、糖原水平和利用率与运动肌肉以及 Na+/K+ 泵送率的影响。

准确量化细胞对静息、激活和患病大脑中底物利用率的贡献对于解释使用 [ 18 F] 氟脱氧葡萄糖正电子发射断层扫描 (FDG-PET) 和 [ 13 ] 的研究数据至关重要C]葡萄糖/磁共振波谱(MRS)。一个普遍接受的教条是神经元对所有脑细胞的能量需求最高,计算出神经元在清醒时的葡萄糖氧化率,静息脑占 70-80%,星形胶质细胞占 20-30%。然而,这些比例没有考虑细胞类型的体积分数。为了评估调整星形胶质细胞体积分数后神经元-星形胶质细胞葡萄糖氧化率相似的结论 (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海马、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分别乘以 17.6、11.4 和 6.8 来调整体积分数。调整后,静息清醒大鼠脑中的星形胶质细胞葡萄糖氧化率比神经元氧化率高 4-10 倍。体积分数调整也会增加脑糖原浓度和利用率,使其接近或超过锻炼肌肉。如果假设星形胶质细胞-神经元体积分数相等,则用于评估神经传递过程中钠/钾稳态的离子通量计算是不正确的。调整体积分数后葡萄糖和糖原的高利用率表明星形胶质细胞的能量需求远大于公认的,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,挑战了星形胶质细胞“喂食”的概念饥饿的神经元”。体积分数调整也会增加脑糖原浓度和利用率,使其接近或超过锻炼肌肉。如果假设星形胶质细胞-神经元体积分数相等,则用于评估神经传递过程中钠/钾稳态的离子通量计算是不正确的。调整体积分数后葡萄糖和糖原的高利用率表明星形胶质细胞的能量需求远大于公认的,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,挑战了星形胶质细胞“喂食”的概念饥饿的神经元”。体积分数调整也会增加脑糖原浓度和利用率,使其接近或超过锻炼肌肉。如果假设星形胶质细胞-神经元体积分数相等,则用于评估神经传递过程中钠/钾稳态的离子通量计算是不正确的。调整体积分数后葡萄糖和糖原的高利用率表明星形胶质细胞的能量需求远大于公认的,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,挑战了星形胶质细胞“喂食”的概念饥饿的神经元”。如果假设星形胶质细胞-神经元体积分数相等,则用于评估神经传递过程中钠/钾稳态的离子通量计算是不正确的。调整体积分数后葡萄糖和糖原的高利用率表明星形胶质细胞的能量需求远大于公认的,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,挑战了星形胶质细胞“喂食”的概念饥饿的神经元”。如果假设星形胶质细胞-神经元体积分数相等,则用于评估神经传递过程中钠/钾稳态的离子通量计算是不正确的。调整体积分数后葡萄糖和糖原的高利用率表明星形胶质细胞的能量需求远大于公认的,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,挑战了星形胶质细胞“喂食”的概念饥饿的神经元”。

更新日期:2020-09-20
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