Oreiro-García M Teresa, Vázquez-Illanes M Dolores, Sierra-Paredes Germán, Sierra-Marcuño Germán
Neuroscience Division, Department of Biochemistry and Molecular Biology, School of Medicine, University of Santiago, San Francisco 1, 15782 Santiago de Compostela, Spain.
Neurochem Int. 2007 Apr;50(5):734-40. doi: 10.1016/j.neuint.2007.01.005. Epub 2007 Jan 20.
The effect of latrunculin A microperfusion on hippocampal extracellular concentrations of glutamate, aspartate, glycine and GABA, as measured by in vivo microdialysis, was investigated. Latrunculin A (4 microg/ml) was perfused for three consecutive days (8h a day) to promote in vivo F-actin depolymerization. Intrahippocampal latrunculin A microdialysis induced seizures during the second and third day of perfusion, and the animals started showing spontaneous seizures 1 month after lartrunculin A administration. Hippocampal glutamate levels were significantly increased during the first day of latrunculin A microperfusion without significant changes during the second and third day of perfusion. Aspartate levels were significantly increased during the first and second days of treatment. The rise on glutamate and asparate levels was partially reversed by perfusion of NMDA antagonist MK-801. Glycine concentrations were significantly increased during the 3 days of latrunculin A microdialyis, but no significant effect was observed on baseline GABA levels. One month after latrunculin A microperfusion, no significant differences in glutamate and aspartate extracellular concentrations were detected as compared to controls, however, significant increases in glycine and GABA extracellular concentrations were observed. The immediate increases in glutamate, aspartate and glycine levels indicate a modulatory effect of the F-actin cytoskeleton on extracellular concentrations of glutamate, aspartate and glycine. The chronic elevations in GABA and glycine levels are more likely to be related with long-term epileptogenesis processes. Our results suggest that the in vivo biochemical study of actin-dependent processes seems to be a promising approach to the neuropathology and neuropharmacology of epileptic seizures.
研究了用体内微透析法测定的拉春库林A微量灌注对海马细胞外谷氨酸、天冬氨酸、甘氨酸和γ-氨基丁酸浓度的影响。连续三天（每天8小时）灌注拉春库林A（4微克/毫升）以促进体内丝状肌动蛋白解聚。海马内微量灌注拉春库林A在灌注的第二天和第三天诱发癫痫发作，并且动物在给予拉春库林A后1个月开始出现自发性癫痫发作。在拉春库林A微量灌注的第一天，海马谷氨酸水平显著升高，而在灌注的第二天和第三天没有显著变化。在治疗的第一天和第二天，天冬氨酸水平显著升高。谷氨酸和天冬氨酸水平的升高被NMDA拮抗剂MK-801的灌注部分逆转。在拉春库林A微量透析的3天中，甘氨酸浓度显著升高，但对基线γ-氨基丁酸水平未观察到显著影响。在拉春库林A微量灌注1个月后，与对照组相比，未检测到谷氨酸和天冬氨酸细胞外浓度的显著差异，然而，观察到甘氨酸和γ-氨基丁酸细胞外浓度显著升高。谷氨酸、天冬氨酸和甘氨酸水平的立即升高表明丝状肌动蛋白细胞骨架对谷氨酸、天冬氨酸和甘氨酸细胞外浓度具有调节作用。γ-氨基丁酸和甘氨酸水平的长期升高更可能与长期癫痫发生过程有关。我们的结果表明，对肌动蛋白依赖性过程的体内生化研究似乎是癫痫发作神经病理学和神经药理学研究的一种有前景的方法。
