Serres Sébastien, Bouyer Jean-Jacques, Bezancon Eric, Canioni Paul, Merle Michel
Unité de Résonance Magnétique des Systèmes Biologiques, UMR 5536, CNRS-Université Victor Segalen, case 93, 146 rue Léo-Saignat, 33076 Bordeaux, France.
NMR Biomed. 2003 Oct-Nov;16(6-7):430-9. doi: 10.1002/nbm.838.
The involvement of brain lactate in neuronal metabolism was analyzed by ex vivo NMR spectroscopy with rats under the effects of pentobarbital, alphachloralose or morphine, which were infused with a solution of either [1-(13)C]glucose+lactate or glucose+[3-(13)C]lactate for 20 min. Electroencephalogram recordings indicated different brain electrical activity levels under the three drugs with a clear distinction between pentobarbital, on the one hand, and alphachloralose and morphine on the other. Labeling of metabolites in brain perchloric acid extracts and of blood glucose and lactate was determined by (13)C- and/or (1)H-observed/(13)C-edited-NMR spectroscopy. The following were found: (i) the ratio between glutamate C3 and C4 (13)C-enrichments increased from pentobarbital to alphachloralose and morphine whatever the labeled precursor, indicating a link between metabolic and electrical activity; (ii) under glucose+[3-(13)C]lactate infusion, alanine C3 and acetyl-CoA C2 enrichments were higher than that of lactate C3, revealing the occurrence of an isotopic dilution of the brain exogenous lactate (arising from blood) by lactate from brain (endogenous lactate); the latter was synthesized from glycolysis in a compartment other than the neurons; (iii) the contributions of labeled glucose and lactate to acetyl-CoA C2 enrichment indicated that the involvement of blood glucose relative to that of blood lactate to brain metabolism was correlated with brain activity. It can therefore be concluded that the brain electrical activity-dependent increase in the contribution of blood glucose relative to that of blood lactate to brain metabolism occurred partly via the increase in the metabolism of lactate generated from astrocytic glycolysis. This conclusion supports the hypothesis of an astrocyte-neuron lactate shuttle component in the coupling mechanism between cerebral activity and energy metabolism.
通过体外核磁共振波谱法，对戊巴比妥、α-氯醛糖或吗啡作用下的大鼠进行分析，研究脑乳酸在神经元代谢中的作用。给这些大鼠输注[1-(13)C]葡萄糖+乳酸溶液或葡萄糖+[3-(13)C]乳酸溶液20分钟。脑电图记录表明，这三种药物作用下的脑电活动水平不同，戊巴比妥与α-氯醛糖和吗啡之间有明显区别。通过(13)C和/或(1)H观测/(13)C编辑核磁共振波谱法测定脑高氯酸提取物中代谢物以及血糖和乳酸的标记情况。结果发现：(i)无论标记前体如何，从戊巴比妥到α-氯醛糖和吗啡，谷氨酸C3和C4的(13)C富集比增加，表明代谢与电活动之间存在联系；(ii)在输注葡萄糖+[3-(13)C]乳酸的情况下，丙氨酸C3和乙酰辅酶A C2的富集高于乳酸C3，这表明脑外源性乳酸（来自血液）被脑内乳酸（内源性乳酸）发生了同位素稀释；后者是在神经元以外的隔室中由糖酵解合成的；(iii)标记葡萄糖和乳酸对乙酰辅酶A C2富集的贡献表明，血糖相对于血乳酸对脑代谢的参与与脑活动相关。因此可以得出结论，脑电活动依赖性地增加血糖相对于血乳酸对脑代谢的贡献，部分是通过星形胶质细胞糖酵解产生的乳酸代谢增加实现的。这一结论支持了星形胶质细胞-神经元乳酸穿梭成分在脑活动与能量代谢耦合机制中的假说。
