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首页> 外文期刊>Neurochemistry International: The International Journal for the Rapid Publication of Critical Reviews, Preliminary and Original Research Communications in Neurochemistry >beta-Hydroxybutyrate is the preferred substrate for GABA and glutamate synthesis while glucose is indispensable during depolarization in cultured GABAergic neurons.
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beta-Hydroxybutyrate is the preferred substrate for GABA and glutamate synthesis while glucose is indispensable during depolarization in cultured GABAergic neurons.

机译:β-羟基丁酸酯是GABA和谷氨酸合成的首选底物,而葡萄糖在培养的GABA能神经元去极化过程中不可或缺。

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摘要

The ketogenic diet has multiple beneficial effects not only in treatment of epilepsy, but also in that of glucose transporter 1 deficiency, cancer, Parkinson's disease, obesity and pain. Thus, there is an increasing interest in understanding the mechanism behind this metabolic therapy. Patients on a ketogenic diet reach high plasma levels of ketone bodies, which are used by the brain as energy substrates. The interaction between glucose and ketone bodies is complex and there is still controversy as to what extent it affects the homeostasis of the neurotransmitters glutamate, aspartate and GABA. The present study was conducted to study this metabolic interaction in cultured GABAergic neurons exposed to different combinations of (13)C-labeled and unlabeled glucose and beta-hydroxybutyrate. Depolarization was induced and the incorporation of (13)C into glutamate, GABA and aspartate was analyzed. The presence of beta-hydroxybutyrate together with glucose did not affect the total GABA content but did, however, decrease the aspartate content to a lower value than when either glucose or beta-hydroxybutyrate was employed alone. When combinations of the two substrates were used (13)C-atoms from beta-hydroxybutyrate were found in all three amino acids to a greater extent than (13)C-atoms from glucose, but only the (13)C contribution from [1,6-(13)C]glucose increased upon depolarization. In conclusion, beta-hydroxybutyrate was preferred over glucose as substrate for amino acid synthesis but the total content of aspartate decreased when both substrates were present. Furthermore only the use of glucose increased upon depolarization.
机译:生酮饮食不仅对癫痫的治疗具有多种有益作用,而且对葡萄糖转运蛋白1缺乏症,癌症,帕金森氏病,肥胖症和疼痛也具有多种有益作用。因此,人们越来越了解这种代谢疗法的机理。生酮饮食的患者血浆中酮体的含量很高,酮被大脑用作能量底物。葡萄糖和酮体之间的相互作用是复杂的,关于它在多大程度上影响神经递质谷氨酸,天冬氨酸和GABA的稳态,仍存在争议。进行本研究以研究暴露于(13)C标记和未标记的葡萄糖与β-羟基丁酸酯的不同组合的培养的GABA能神经元中的这种代谢相互作用。诱导去极化并分析了将(13)C掺入谷氨酸,GABA和天冬氨酸中。与单独使用葡萄糖或β-羟基丁酸酯的情况相比,β-羟基丁酸酯与葡萄糖的存在不会影响总GABA含量,但确实将天冬氨酸的含量降低至更低的值。当使用两种底物的组合时,在所有三个氨基酸中发现(13)C-原子来自β-羟基丁酸酯的程度要比来自葡萄糖的(13)C-原子更大,但只有[1]的(13)C贡献。 ,6-(13)C]葡萄糖在去极化时增加。总之,β-羟基丁酸酯优于葡萄糖作为氨基酸合成的底物,但是当同时存在两种底物时,天冬氨酸的总含量降低。此外,去极化后仅葡萄糖的使用增加。

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