In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics

In vivo nuclear magnetic resonance spectroscopy studies of the relationship between the glutamate-glutamine neurotransmitter cycle and functional neuroenergetics
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DOI:
10.1098/rstb.1999.0472
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发表时间:
1999-07-29
影响因子:
6.3
通讯作者:
Shulman, RG
Shulman, RG
中科院分区:
生物学1区
文献类型:
--
作者:
Rothman, DL;Sibson, NR;Shulman, RG

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在这篇文章中,我们回顾了最近的研究,主要是从我们的实验室,使用C-13 NMR(核磁共振),以非侵入性测量大鼠和人类皮层中的谷氨酸-谷氨酰胺神经递质循环的速率。在谷氨酸-谷氨酰胺循环中,从神经末梢释放的谷氨酸被周围的神经胶质细胞吸收,并以谷氨酰胺的形式返回到神经末梢。C-13 NMR研究表明,谷氨酸-谷氨酰胺循环的速率在大鼠和人类皮质中都非常高,并且随着大脑活动的增加,其与氧化葡萄糖代谢的摩尔比约为1:1。测量的比率,结合P. J. Magistretti及其同事基于分离细胞研究的建议,导致了一种模型的开发,其中大部分脑葡萄糖氧化与谷氨酸-谷氨酰胺循环机械耦合。该模型提供了皮质葡萄糖代谢和特定神经元活动之间的第一个可测试的机制关系。在这里,我们审查这个模型的实验证据,以及对血氧水平依赖的磁共振成像和正电子发射断层扫描功能成像研究的脑功能的影响。
In this article we review recent studies, primarily from our laboratory, using C-13 NMR (nuclear magnetic resonance) to non-invasively measure the rate of the glutamate-glutamine neurotransmitter cycle in the cortex of rats and humans. In the glutamate-glutamine cycle, glutamate released from nerve terminals is taken up by surrounding glial cells and returned to the nerve terminals as glutamine. C-13 NMR studies have shown that the rate of the glutamate-glutamine cycle is extremely high in both the rat and human cortex, and that it increases with brain activity in an approximately 1:1 molar ratio with oxidative glucose metabolism. The measured ratio, in combination with proposals based on isolated cell studies by P.J. Magistretti and co-workers, has led to the development of a model in which the majority of brain glucose oxidation is mechanistically coupled to the glutamate-glutamine cycle. This model provides the first testable mechanistic relationship between cortical glucose metabolism and a specific neuronal activity. We review here the experimental evidence for this model as well as implications for blood oxygenation level dependent magnetic resonance imaging and positron emission tomography functional imaging studies of brain function.