Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy:: Elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism
Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy:: Elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism
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DOI：
10.1523/jneurosci.22-05-01523.2002
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发表时间：
2002-03-01
影响因子：
5.3
通讯作者：
Rothman, DL
中科院分区：
文献类型：
--
作者：
Lebon, V;Petersen, KF;Rothman, DL
越来越多的证据支持神经胶质代谢在维持适当的突触功能和神经系统疾病的病因学中的关键作用。然而，由于缺乏非侵入性方法，人类神经胶质代谢的研究一直受到阻碍。为了具体测量星形胶质细胞对人类大脑能量代谢的贡献，我们使用了一种新的非侵入性核磁共振光谱方法。我们测量了8名志愿者在静脉注射[2-C-13]醋酸酯期间大脑谷氨酸和谷氨酰胺中的碳13掺入量，动物模型表明，乙酸盐在星形胶质细胞中特定代谢。对已建立的三条神经递质谷氨酸补充途径的数学模拟表明，星形胶质细胞和神经元之间的谷氨酸/谷氨酰胺神经递质循环(0.32+/-0.07mumol·gm(-1).min(-1))是神经元谷氨酸补充的主要途径，星形胶质细胞TCA循环通量(0.14+/-0.06mumol.gm(-1).min(-1))约占脑耗氧量的14%。在这个循环中，高达30%的谷氨酰胺转移到神经元中，可能来自于倒置取代氧化的谷氨酸。这一方法的进一步应用可能会启发星形胶质细胞在支持大脑谷氨酸能活动以及在神经和精神疾病中的作用。
Increasing evidence supports a crucial role for glial metabolism in maintaining proper synaptic function and in the etiology of neurological disease. However, the study of glial metabolism in humans has been hampered by the lack of noninvasive methods. To specifically measure the contribution of astroglia to brain energy metabolism in humans, we used a novel noninvasive nuclear magnetic resonance spectroscopic approach. We measured carbon 13 incorporation into brain glutamate and glutamine in eight volunteers during an intravenous infusion of [2-C-13] acetate, which has been shown in animal models to be metabolized specifically in astroglia. Mathematical modeling of the three established pathways for neurotransmitter glutamate repletion indicates that the glutamate/glutamine neurotransmitter cycle between astroglia and neurons (0.32+/-0.07 mumol.gm(-1).min(-1)) is the major pathway for neuronal glutamate repletion and that the astroglial TCA cycle flux (0.14+/-0.06 mumol.gm(-1).min(-1)) accounts for similar to14% of brain oxygen consumption. Up to 30% of the glutamine transferred to the neurons by the cycle may derive from replacement of oxidized glutamate by anaplerosis. The further application of this approach could potentially enlighten the role of astroglia in supporting brain glutamatergic activity and in neurological and psychiatric disease.