肿瘤坏死因子 (TNF) 在神经炎症性疾病中具有明确的作用，但 TNF 对脑细胞生化的影响仍知之甚少。在这里，我们将 TNF 显微注射到大脑中，使用 13C NMR 光谱对静脉注射后的脑提取物进行研究，以研究其对神经胶质和神经元代谢（糖酵解、磷酸戊糖途径、柠檬酸循环、丙酮酸脱氢酶和丙酮酸羧化酶途径）的影响 [1,2- 13C]-葡萄糖（用于探测神经胶质细胞和神经元代谢）、[2-13C]-乙酸盐（探测星形胶质细胞特异性代谢物）或[3-13C]-乳酸。 [1,2-13C]-葡萄糖中观察到[4,5-13C]-谷氨酰胺和[2,3-13C]-乳酸增加，同时[4,5-13C]-谷氨酸减少。用 TNF 治疗的输注动物。由于谷氨酰胺是由星形胶质细胞特异性谷氨酰胺合成酶从谷氨酸产生的，[4,5-13C]-谷氨酰胺的增加反映了星形胶质细胞谷氨酰胺产量的增加。通过输注星形胶质细胞底物[2-13C]-乙酸盐证实了这一点。由于乳酸在大脑中代谢产生谷氨酸，[2,3-13C]-乳酸同时增加和[4,5-13C]-谷氨酸减少表明乳酸利用率降低，这一点已通过[3-13C]证实-乳酸作为代谢前体。这些结果表明 TNF 重新排列代谢网络，扰乱能量供应链，扰乱星形胶质细胞和神经元之间的谷氨酰胺-谷氨酸穿梭。这些见解为开发星形胶质细胞靶向治疗策略铺平了道路，该策略旨在调节 TNF 的作用以恢复神经炎症性疾病的代谢稳态。

Tumor necrosis factor (TNF) has well-established roles in neuroinflammatory disorders, but the effect of TNF on the biochemistry of brain cells remains poorly understood. Here, we microinjected TNF into the brain to study its impact on glial and neuronal metabolism (glycolysis, pentose phosphate pathway, citric acid cycle, pyruvate dehydrogenase, and pyruvate carboxylase pathways) using 13C NMR spectroscopy on brain extracts following intravenous [1,2-13C]-glucose (to probe glia and neuron metabolism), [2-13C]-acetate (probing astrocyte-specific metabolites), or [3-13C]-lactate. An increase in [4,5-13C]-glutamine and [2,3-13C]-lactate coupled with a decrease in [4,5-13C]-glutamate was observed in the [1,2-13C]-glucose-infused animals treated with TNF. As glutamine is produced from glutamate by astrocyte-specific glutamine synthetase the increase in [4,5-13C]-glutamine reflects increased production of glutamine by astrocytes. This was confirmed by infusion with astrocyte substrate [2-13C]-acetate. As lactate is metabolized in the brain to produce glutamate, the simultaneous increase in [2,3-13C]-lactate and decrease in [4,5-13C]-glutamate suggests decreased lactate utilization, which was confirmed using [3-13C]-lactate as a metabolic precursor. These results suggest that TNF rearranges the metabolic network, disrupting the energy supply chain perturbing the glutamine-glutamate shuttle between astrocytes and the neurons. These insights pave the way for developing astrocyte-targeted therapeutic strategies aimed at modulating effects of TNF to restore metabolic homeostasis in neuroinflammatory disorders.