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大脑中能量代谢的细胞途径:葡萄糖是被神经元还是星形胶质细胞利用?

Cellular pathways of energy metabolism in the brain: is glucose used by neurons or astrocytes?

作者信息

Nehlig Astrid, Coles Jonathan A

机构信息

INSERM U 666, Faculty of Medicine, Strasbourg, France.

INSERM Unité 594, Functional and Metabolic Neuroimaging, Université Joseph Fourier, Grenoble, France.

出版信息

Glia. 2007 Sep;55(12):1238-1250. doi: 10.1002/glia.20376.

DOI:10.1002/glia.20376
PMID:17659529
Abstract

Most techniques presently available to measure cerebral activity in humans and animals, i.e. positron emission tomography (PET), autoradiography, and functional magnetic resonance imaging, do not record the activity of neurons directly. Furthermore, they do not allow the investigator to discriminate which cell type is using glucose, the predominant fuel provided to the brain by the blood. Here, we review the experimental approaches aimed at determining the percentage of glucose that is taken up by neurons and by astrocytes. This review is integrated in an overview of the current concepts on compartmentation and substrate trafficking between astrocytes and neurons. In the brain in vivo, about half of the glucose leaving the capillaries crosses the extracellular space and directly enters neurons. The other half is taken up by astrocytes. Calculations suggest that neurons consume more energy than do astrocytes, implying that astrocytes transfer an intermediate substrate to neurons. Experimental approaches in vitro on the honeybee drone retina and on the isolated vagus nerve also point to a continuous transfer of intermediate metabolites from glial cells to neurons in these tissues. Solid direct evidence of such transfer in the mammalian brain in vivo is still lacking. PET using [(18)F]fluorodeoxyglucose reflects in part glucose uptake by astrocytes but does not indicate to which step the glucose taken up is metabolized within this cell type. Finally, the sequence of metabolic changes occurring during a transient increase of electrical activity in specific regions of the brain remains to be clarified.

摘要

目前可用于测量人类和动物大脑活动的大多数技术,即正电子发射断层扫描(PET)、放射自显影和功能磁共振成像,都不能直接记录神经元的活动。此外,它们也无法让研究人员区分哪种细胞类型正在利用葡萄糖,而葡萄糖是血液为大脑提供的主要能量来源。在此,我们综述了旨在确定神经元和星形胶质细胞摄取葡萄糖百分比的实验方法。本综述融入了对星形胶质细胞和神经元之间分隔及底物转运的当前概念的概述。在活体大脑中,离开毛细血管的葡萄糖约有一半穿过细胞外空间并直接进入神经元。另一半则被星形胶质细胞摄取。计算结果表明,神经元比星形胶质细胞消耗更多能量,这意味着星形胶质细胞会将一种中间底物转运给神经元。在蜜蜂雄蜂视网膜和离体迷走神经上进行的体外实验方法也表明,在这些组织中存在中间代谢物从神经胶质细胞持续转移至神经元的现象。在哺乳动物活体大脑中仍缺乏这种转移的确凿直接证据。使用[(18)F]氟脱氧葡萄糖的PET部分反映了星形胶质细胞对葡萄糖的摄取,但并未表明摄取的葡萄糖在该细胞类型内代谢到哪一步。最后,大脑特定区域电活动短暂增加期间发生的代谢变化序列仍有待阐明。

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