Glial‐Neuronal Interactions as Studied by Cerebral Metabolism of [2‐13C]Acetate and [1‐13C]Glucose: An Ex Vivo 13C NMR Spectroscopic Study
Glial‐Neuronal Interactions as Studied by Cerebral Metabolism of [2‐13C]Acetate and [1‐13C]Glucose: An Ex Vivo 13C NMR Spectroscopic Study
复制标题
通过[2-13C]乙酸和[1-13C]葡萄糖的脑代谢研究胶质细胞-神经元相互作用：体外 13C NMR 波谱研究
DOI：
10.1046/j.1471-4159.1995.64062773.x
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发表时间：
1995
影响因子：
4.7
通讯作者：
F. Fonnum
中科院分区：
文献类型：
--
作者：
B. Hassel;U. Sonnewald;F. Fonnum
摘要：小鼠静脉注射[2 - 13 C]-醋酸盐或[1 - 13 C]葡萄糖，并在5、15或30 min后处死。另一组动物在30 min内皮下注射3次[2 - 13 C]醋酸盐，以达到类似稳态的情况。脑提取物进行了分析，13 C NMR光谱，并计算了氨基酸，乳酸盐和葡萄糖的各种碳位置的富集百分比。用[2 - 13 C]乙酸盐（由神经胶质代谢而不是神经元代谢）获得的结果表明，谷氨酰胺源自神经胶质三羧酸循环（TCA循环），该循环每转损失65%的中间产物。该TCA循环与丙酮酸羧化相关，这可以补充几乎所有的这种损失，如从[1 - 13 C]葡萄糖标记谷氨酰胺所见。从谷氨酰胺和谷氨酸中的C-3/C-4标记比率以及从用[2 - 13 C]乙酸盐获得的GABA中的相应C-3/C-2标记比率，可以得出结论，在谷氨酸和GABA形成之前，谷氨酰胺的碳骨架在一定程度上通过TCA循环。因此，星形胶质细胞衍生的谷氨酰胺不仅是递质氨基酸的前体，而且也是体内神经元的能量底物。此外，神经元TCA循环可能是递质氨基酸合成的控制点。注射[2 - 13 C]乙酸盐导致谷氨酸盐中C-2和GABA中相应C-4的13 C富集高于任一化合物的C-3。这可能反映了[2 - 13 C]-柠檬酸的裂解和[3 - 13 C]草酰乙酸和乙酰辅酶A的形成，即，脂肪酸合成的第一步。[3 - 13 C]-草酰乙酸在进入TCA循环后，将给出观察到的谷氨酸和GABA标记。
Abstract: Mice were injected intravenously with [2‐13C]‐acetate or [1‐13C]glucose and killed after 5, 15, or 30 min. Another group of animals was injected three times subcutaneously during 30 min with [2‐13C]acetate to achieve a steady‐state‐like situation. Brain extracts were analyzed by 13C NMR spectroscopy, and the percent enrichment of various carbon positions was calculated for amino acids, lactate, and glucose. Results obtained with [2‐13C]acetate, which is metabolized by glia and not by neurons, showed that glutamine originated from a glial tricarboxylic acid cycle (TCA cycle) that loses 65% of its intermediates per turn of the cycle. This TCA cycle was associated with pyruvate carboxylation, which may replenish virtually all of this loss, as seen from the labeling of glutamine from [1‐13C]glucose. From the C‐3/C‐4 labeling ratios in glutamine and glutamate and from the corresponding C‐3/C‐2 labeling ratio in GABA obtained with [2‐13C]acetate, it was concluded that the carbon skeleton of glutamine to some extent was passed through TCA cycles before glutamate and GABA were formed. Thus, astrocytically derived glutamine is not only a precursor for transmitter amino acids but is also an energy substrate for neurons in vivo. Furthermore, the neuronal TCA cycles may be control points in the synthesis of transmitter amino acids. Injection of [2‐13C]acetate led to a higher 13C enrichment of the C‐2 in glutamate and of the corresponding C‐4 in GABA than in the C‐3 of either compound. This could reflect cleavage of [2‐13C]‐citrate and formation of [3‐13C]oxaloacetate and acetyl‐CoA, i.e., the first step in fatty acid synthesis. [3‐13C]‐Oxaloacetate would, after entry into a TCA cycle, give the observed labeling of glutamate and GABA.