Changes of glial-neuronal interaction and metabolism after a subconvulsive dose of pentylenetetrazole
Changes of glial-neuronal interaction and metabolism after a subconvulsive dose of pentylenetetrazole
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DOI：
10.1016/j.neuint.2004.02.002
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发表时间：
2004-10-01
影响因子：
4.2
通讯作者：
Sonnewald, U
中科院分区：
文献类型：
--
作者：
Eloqayli, H;Dahl, CB;Sonnewald, U
戊四唑（PTZ）注射导致啮齿动物癫痫发作，并用于几种癫痫模型。在本研究中，将低剂量（20 mg/kg）注射到大鼠体内，以分析亚惊厥量PTZ引起的代谢紊乱。腹腔注射PTZ后，30分钟后，注射[1-C-13]葡萄糖加[1，2-C-13]乙酸盐，15分钟后断头。用C-13核磁共振波谱和高效液相色谱法对大脑、皮质下和小脑的提取物进行了分析。而惊厥剂量的PTZ导致小脑中最显著的变化[J. Neurochem. 85（2003）1200]，可以表明亚惊厥剂量主要影响大脑中的氨基酸代谢。在大脑中的谷氨酸能神经元中，PTZ影响谷氨酸的代谢池和可释放池，而在皮质下和小脑中，仅代谢池受到影响。这可以从以下发现中推断：在该区域检测到较少的[4-C-13]谷氨酰胺、[3，4-C-13]谷氨酸和[2-C-13]天冬氨酸（由[1-C-13]葡萄糖标记）。胶质细胞的代谢也发生了变化，表现为大脑和皮层下丙酮酸羧化与丙酮酸脱氢的比率降低。惊厥和非惊厥剂量的PTZ之间的比较导致的假设，观察到的变化，小脑主要是由于癫痫发作，而那些在大脑和皮质下的耦合的化学兴奋剂的作用。(C)2004爱思唯尔有限公司保留所有权利。
Pentylenetetrazole (PTZ) injection causes seizures in rodents and this is used in several models of epilepsy. In the present study a low dose (20 mg/kg) was injected into rats in order to analyze metabolic disturbances caused by subconvulsive amounts of PTZ. Intraperitoneal injection of PTZ was followed, 30 min later, by injection of [1-C-13]glucose plus [1,2-C-13]acetate and 15 min thereafter decapitation. Analyses of extracts from cerebrum, subcortex and cerebellum were performed using C-13 NMRS and HPLC. Whereas convulsive doses of PTZ lead to most pronounced changes in cerebellum [J. Neurochem. 85 (2003) 1200], it could be shown that subconvulsive doses affected mainly amino acid metabolism in cerebrum. In glutamatergic neurons in the cerebrum PTZ affected both the metabolic and releasable pools of glutamate, whereas, in the subcortex and cerebellum only the metabolic pool was affected. This could be deducted from the findings that less [4-C-13]glutamine, [3,4-C-13]glutamate and [2-C-13]aspartate, which are labeled from [1-C-13]glucose, were detected in this area. Glial metabolism was also changed as evidenced by the decreased pyruvate carboxylation versus pyruvate dehydrogenation ratio both in cerebrum and subcortex. Comparison between convulsive and nonconvulsive doses of PTZ lead to the hypothesis that changes observed in the cerebellum are mainly due to seizures, whereas those in cerebrum and subcortex are coupled to the action of the chemical stimulant. (C) 2004 Elsevier Ltd. All rights reserved.