Cellular mechanisms of brain energy metabolism - Relevance to functional brain imaging and to neurodegenerative disorders
Cellular mechanisms of brain energy metabolism - Relevance to functional brain imaging and to neurodegenerative disorders
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DOI：
10.1111/j.1749-6632.1996.tb34449.x
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发表时间：
1996-01-01
期刊：
影响因子：
--
通讯作者：
Pellerin, L
中科院分区：
文献类型：
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作者：
Magistretti, PJ;Pellerin, L
星形胶质细胞终足围绕实质内微血管，因此代表葡萄糖进入脑的第一个细胞屏障。因此，它们是普遍葡萄糖摄取的可能位点。星形胶质细胞过程也包裹在突触接触周围，这意味着它们被理想地定位为感测并在功能上与增加的突触活动耦合。我们最近已经证明，谷氨酸，主要的兴奋性神经递质，刺激2-DG摄取和磷酸化的星形胶质细胞在原代培养中的浓度依赖性方式。(1)这种作用不是受体介导的，而是通过最近克隆的谷氨酸转运蛋白之一进行的。该机制涉及Na+/K+ ATP酶的激活。伴随着葡萄糖摄取的刺激，谷氨酸导致乳酸流出的浓度依赖性增加。这些观察结果表明，谷氨酸摄取耦合到有氧糖酵解星形胶质细胞。此外，由于谷氨酸释放发生在脑区域的模态特异性激活之后，谷氨酸诱发的葡萄糖摄取到星形胶质细胞中提供了将神经元活性与能量代谢偶联的简单机制。这些数据还表明，使用基于2DG的放射自显影或PET可视化的模态特异性激活可能主要反映谷氨酸介导的2DG摄取到星形胶质细胞中。
Astrocyte end-feet surround intraparenchymal microvessels and represent therefore the first cellular barrier for glucose entering the brain. As such, they are a likely site of prevalent glucose uptake. Astrocytic processes are also wrapped around synaptic contacts, implying that they are ideally positioned to sense and be functionally coupled to increased synaptic activity. We have recently demonstrated that glutamate, the main excitatory neurotransmitter, stimulates in a concentration-dependent manner 2-DG uptake and phosphorylation by astrocytes in primary culture.(1) The effect is not receptor-mediated but rather proceeds via one of the recently cloned glutamate transporter. The mechanism involves an activation of the Na+/K+ ATPase. Concomitant to the stimulation of glucose uptake, glutamate causes a concentration-dependent increase in lactate efflux. These observations suggest that glutamate uptake is coupled to aerobic glycolysis in astrocytes. In addition, since glutamate release occurs following the modality-specific activation of a brain region, the glutamate-evoked uptake of glucose into astrocytes provides a simple mechanism to couple neuronal activity to energy metabolism. These data also suggest that modality-specific activation visualized using 2DG-based autoradiography or PET may primarily reflect glutamate-mediated uptake of 2DG into astrocytes.