Glutamate-glutamine cycling in the epileptic human hippocampus
Glutamate-glutamine cycling in the epileptic human hippocampus
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DOI：
10.1046/j.1528-1157.2002.38901.x
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发表时间：
2002-07-01
期刊：
影响因子：
5.6
通讯作者：
Spencer, DD
中科院分区：
文献类型：
--
作者：
Petroff, OAC;Errante, LD;Spencer, DD
目的：一些研究结果表明，癫痫患者的能量代谢和谷氨酸-谷氨酰胺循环可能受损。正电子发射断层扫描常显示癫痫发作间期海马代谢减退。体内微透析研究表明，与糖尿病相关的谷氨酸释放增加一倍，清除减慢。我们假设，神经元和胶质细胞之间的谷氨酸-谷氨酰胺循环可能会减少在癫痫hippocamps.Methods：A 20%的2-C-13-葡萄糖溶液被注入前切除致癫痫海马。每30分钟测量一次血糖同位素分数。血液和脑标本迅速冷冻;高氯酸提取物的小代谢产物的制备和分析质子和碳磁共振光谱（MRS）在11.75 Tesla.Results：标准组织学显示12海马硬化和5个最小的神经元损失。与最小神经元丢失组（0.52; 95%CI，0.30-0.75）相比，受海马硬化影响的活检组织中谷氨酸-谷氨酰胺循环相对于谷氨酸合成的相对速率降低（平均值，0.08; 95%置信区间，0.04-0.12）。在最小神经元损失（8.9 mM; 95% CI，7.4-10.4）中的平均细胞谷氨酸浓度高于海马硬化（7.3 mM; 95% CI，5.9-8.7）。细胞谷氨酰胺浓度（平均值，2.8 mM; 95% CI，2.4-3.2; n = 17）是相同的，在所有group.Conclusions：癫痫，神经胶质化的人海马出现代谢的特点是缓慢的谷氨酸-谷氨酰胺循环，谷氨酰胺含量下降，谷氨酸含量相对增加。我们推测，低速率的谷氨酸-谷氨酰胺循环，从胶质细胞谷氨酸解毒失败的结果可以解释缓慢的谷氨酸清除突触和持续的低度兴奋性毒性。
Purpose: Several findings suggest that energy metabolism and the glutamate-glutamine cycle may be impaired in epilepsy. Positron emission tomography often shows interictal hypometabolism of the epileptogenic hippocampus. In vivo microdialysis studies show that seizure-associated glutamate release is doubled, and clearance is slowed. We hypothesized that the glutamate-glutamine cycle between neurons and glia may be decreased in the epileptic human hippocampus.Methods: A 20% solution of 2-C-13-glucose was infused before resection of the epileptogenic hippocampus. Blood glucose isotopic fractions were measured every 30 min. Blood and brain specimens were frozen quickly; perchloric acid extracts of the small metabolites were prepared and analyzed by proton and carbon magnetic resonance spectroscopy (MRS) at 11.75 Tesla.Results: Standard histology showed 12 with hippocampal sclerosis and five with minimal neuron loss. The relative rates of glutamate-glutamine cycling with respect to glutamate synthesis were decreased in biopsies affected by hippocampal sclerosis (mean, 0.08; 95% confidence interval, 0.04-0.12) compared with those with minimal neuron loss (0.52; 95% Cl, 0.30-0.75). Mean cellular glutamate concentrations were higher in minimal neuron loss (8.9 mM; 95% CI, 7.4-10.4) than hippocampal sclerosis (7.3 mM; 95% CI, 5.9-8.7). Cellular glutamine concentrations (mean, 2.8 mM; 95% CI, 2.4-3.2; n = 17) were the same in all groups.Conclusions: The epileptogenic, gliotic human hippocampus appears to be characterized metabolically by slow rates of glutamate-glutamine cycling, decreased glutamine content, and a relative increase in glutamate content. We hypothesize that the low rate of glutamate-glutamine cycling that results from a failure of glial glutamate detoxification could account for slow glutamate clearance from synapses and continuing low-grade excitotoxicity.