Cerebral pyruvate carboxylase flux is unaltered during bicuculline-seizures.
Cerebral pyruvate carboxylase flux is unaltered during bicuculline-seizures.
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荷包牡丹碱癫痫发作期间，大脑丙酮酸羧化酶通量没有改变。
DOI：
10.1002/jnr.20311
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Behar,KevinL
中科院分区：
文献类型：
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作者：
Patel,AnantB;Chowdhury,GolamMI;deGraaf,RobinA;Rothman,DouglasL;Shulman,RobertG;Behar,KevinL
星形胶质细胞中的谷氨酰胺合成反映了神经递质循环（谷氨酸和氨基丁酸[GABA]）和从头合成（回补）的总和，后者由丙酮酸羧化酶催化。以前的研究表明，谷氨酸加GABA循环流量与神经元活动密切相关，然而，丙酮酸羧化酶流量和神经元活动之间的关系尚不清楚。在这项研究中，在氟烷麻醉和通气的成年Wistar大鼠中，在荷包牡丹碱诱导的癫痫发作（1 mg/kg，静脉内）的85分钟期间，使用7特斯拉的局部1H-[13 C] NMR光谱法在体内评估了[2- 13 C]葡萄糖静脉输注期间的丙酮酸羧化酶通量，并在未处理的对照组中进行了评估。在癫痫发作期间，乳酸、丙氨酸、谷氨酰胺、GABA和琥珀酸的浓度增加，而谷氨酸和天冬氨酸的浓度降低，使得谷氨酸加天冬氨酸的减少等于谷氨酰胺加GABA的增加。丙酮酸羧化酶通量通过[2 - 13 C]葡萄糖输注期间谷氨酰胺和谷氨酸（Glx 23）标记的[2- 13 C]和[3- 13 C]的总和来评估。在癫痫发作期间，Glx 23合成的初始速率（0.069 - 0.013 mol/g/min）与对照组（0.059 - 0.010 mol/g/min）无显著差异（P 0.68），表明通过丙酮酸羧化酶的回补流未改变。癫痫发作的强烈神经元激活似乎没有通过丙酮酸羧化酶增加回补，尽管在先前的研究中显示了神经元活性和谷氨酸/谷氨酰胺循环的实质性增加（Patel等人，© 2004 Wiley-Liss，Inc.
Glutamine synthesis in the astroglia reflects the sum of neurotransmitter cycling (glutamate and-aminobutyric acid [GABA]) and de novo synthesis (anaplerosis), the latter catalyzed by pyruvate carboxylase. Previous studies have shown that the glutamate plus GABA cycling flux is correlated strongly with neuronal activity; however, the relationship between pyruvate carboxylase flux and neuronal activity is not known. In this study, pyruvate carboxylase flux was assessed during intravenous infusion of [2-13C] glucose using localized 1H-[13C] NMR spectroscopy at 7 Tesla in vivo in halothaneanesthetized and ventilated adult Wistar rats during 85 min of bicuculline-induced seizures (1 mg/kg, intravenously) and in nontreated controls. During seizures, concentrations of lactate, alanine, glutamine, GABA, and succinate increased whereas glutamate and aspartate decreased such that the decrease in glutamate plus aspartate equaled the increase in glutamine plus GABA. Pyruvate carboxylase flux was assessed by the sum of [2-13C] and [3-13C] of glutamine and glutamate (Glx23) labeling during [2-13C] glucose infusion. During seizures the initial rate of Glx23 synthesis (0.069 0.013 mol/g/min) was not significantly different (P 0.68) from that of the controls (0.059 0.010 mol/g/min), indicating that anaplerotic flow through pyruvate carboxylase was unaltered. Intense neuronal activation of seizures did not seem to increase anaplerosis through pyruvate carboxylase, despite the substantial increase in neuronal activity and glutamate/glutamine cycling shown in a previous study (Patel et al., 2004b).© 2004 Wiley-Liss, Inc.