Szyndler Janusz, Maciejak Piotr, Turzyńska Danuta, Sobolewska Alicja, Lehner Małgorzata, Taracha Ewa, Walkowiak Jerzy, Skórzewska Anna, Wisłowska-Stanek Aleksandra, Hamed Adam, Bidziński Andrzej, Płaźnik Adam
Department of Experimental and Clinical Pharmacology, Medical University of Warsaw, 26/28 Krakowskie Przedmieście Street, 00-927 Warsaw, Poland.
Neurosci Lett. 2008 Jul 18;439(3):245-9. doi: 10.1016/j.neulet.2008.05.002. Epub 2008 May 7.
It is not well recognized how disturbances in the local metabolism of some amino acids, especially glutamate and GABA, may lead to seizures. In the presented study, we have examined changes in the hippocampal steady state concentrations of amino acids involved in pentylenetetrazole-kindled and freely moving rats. It was found that in the kindled animals, the concentration of alanine, arginine, glutamate, aspartate and taurine was increased in the interictal period of seizures compared to the control group, whereas kindling reduced the extracellular levels of GABA. No differences between kindled and not-kindled animals in the glycine, histidine and glutamine levels were present. There also appeared an over fourfold increase of the Glu/GABA ratio, a theoretical marker of the neuronal excitation level, in the kindled animals. A multivariate classification tree analysis showed that the hippocampal concentration of taurine, together with GABA and Glu, had the relatively largest prediction accuracy in discriminating between kindled and non-kindled animals, suggesting a specific role of these amino acids in the shaping of a new equilibrium between excitatory and inhibitory processes in the hippocampus of kindled animals.
目前尚不清楚某些氨基酸（尤其是谷氨酸和γ-氨基丁酸）的局部代谢紊乱如何导致癫痫发作。在本研究中，我们检测了戊四氮点燃的自由活动大鼠海马中参与氨基酸稳态浓度的变化。结果发现，与对照组相比，在点燃动物癫痫发作的发作间期，丙氨酸、精氨酸、谷氨酸、天冬氨酸和牛磺酸的浓度升高，而点燃降低了细胞外γ-氨基丁酸水平。在甘氨酸、组氨酸和谷氨酰胺水平上，点燃动物与未点燃动物之间没有差异。在点燃动物中，神经元兴奋水平的理论标志物谷氨酸/γ-氨基丁酸比值也出现了四倍以上的增加。多变量分类树分析表明，牛磺酸、γ-氨基丁酸和谷氨酸的海马浓度在区分点燃动物和未点燃动物方面具有相对最大的预测准确性，这表明这些氨基酸在点燃动物海马兴奋性和抑制性过程之间形成新平衡中具有特定作用。
