Persistent depolarization and Glu uptake inhibition operate distinct osmoregulatory mechanisms in the mammalian brain
Persistent depolarization and Glu uptake inhibition operate distinct osmoregulatory mechanisms in the mammalian brain
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DOI：
10.1016/s0197-0186(00)00020-6
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发表时间：
2000-08-01
影响因子：
4.2
通讯作者：
Kardos, J
中科院分区：
文献类型：
--
作者：
Kékesi, KA;Szilágyi, N;Kardos, J
本文通过微透析实验监测麻醉大鼠脑细胞外氨基酸浓度，探讨了自然生理条件下神经元与胶质细胞间的耦合方式。我们假设细胞外[Glu]、[Gln]和[Tau]模式是状态依赖性的。这通过刺激N-甲基-D-谷氨酸（NMDA）受体、抑制Glu摄取或用高K（+）透析液局部去极化，加上加入Co（2+）阻断Ca（2+）内流来测试。结果表明：（1）NMDA注入时，细胞外[Gln]降低，[Glu]和[Tau]升高（2）海马细胞外[Glu]、[Gln]和[Tau]在Glu摄取抑制剂L-反式-吡咯烷-2，4-二羧酸（L-trans-pyrrolidine-2，4-dicarboxylic acid）作用下增加（tPDC，0.5-3.0 InM），以浓度依赖性方式，（3）高K（+）诱导的细胞外[Glu]增加被加入10 mM CoCl部分阻断（2）与高K（+）透析液在海马中。通过计算偏相关和使用因子分析来寻找[Glu]、[Gln]和[Tau]变化之间的主要相关性，我们发现哺乳动物脑对持续去极化的主要反应是神经元对[Gln]的摄取和随之释放的[Tau]，其作用独立于Glu的变化。当神经胶质和神经元对Glu的摄取被阻断时，在哺乳动物脑中，Tau从神经元和神经胶质隔室中释放，伴随[Gln]的增加。(C)2000爱思唯尔科技有限公司版权所有。
The ways of coupling neuronal with glial compartments in natural physiology was investigated in microdialysis experiments by monitoring extracellular concentration of amino acids in the brain of anaesthetized rats. We hypothesized that extracellular [Glu], [Gln] and [Tau] patterns would be state-dependent, This was tested by stimulation of N-methyl-D-aspartale (NMDA) receptors, by inhibition of Glu uptake or by local depolarization with a high-K(+) dialysate, coupled with the addition of Co(2+) to block Ca(2+) influx. The results showed that (1) extracellular [Gln] was low whereas [Glu] and [Tau] were high during infusion of NMDA (0.5-1.0 mM) or high-K(+) (80 mM) in the hippocampus and ventrobasal thalamus, (2) hippocampal extracellular [Glu], [Gln] and [Tau] were increased in response to the Glu uptake inhibitor, L-trans-pyrrolidine-2,4-dicarboxilic acid (tPDC, 0.5-3.0 InM), in a concentration-dependent manner, (3) high-K(+)-induced increase of extracellular [Glu] was partially blocked by the addition of 10 mM CoCl(2) with the high-K(+) dialysate in the hippocampus. Searching for main correlations between changes in [Glu], [Gln] and [Tau] by calculating partial correlations and with the use of factor analyses we found, the primary response of the mammalian brain to persistent depolarization is the neuronal uptake of [Gln] and release of [Tau] thereupon, acting independently of Glu changes. When glial and neuronal uptake of Glu is blocked, releases of Tau occur from neuronal as well as glial compartments accompanied by increases of [Gln] in the mammalian brain. (C) 2000 Elsevier Science Ltd. All rights reserved.