Raiteri Luca, Stigliani Sara, Zappettini Simona, Mercuri Nicola B, Raiteri Maurizio, Bonanno Giambattista
Department of Experimental Medicine, Pharmacology and Toxicology Section, University of Genoa, Viale Cembrano 4, Genoa 16148, Italy.
Neuropharmacology. 2004 May;46(6):782-92. doi: 10.1016/j.neuropharm.2003.11.025.
The release of [3H]D-aspartate ([3H]D-ASP) or [3H]GABA evoked by glycine and that of [3H]D-ASP or [3H]glycine evoked by GABA from spinal cord synaptosomes were studied in SOD1-G93A(+) mice, a transgenic model of amyotrophic lateral sclerosis, SOD1(+) mice and SOD1(-)/G93A(-) animals. Mutant mice were killed at advanced phase of pathology or during the presymptomatic period. In SOD1(-)/G93A(-) or SOD1(+) mice glycine evoked [(3)H]d-ASP and [(3)H]GABA release, while GABA caused [3H]D-ASP, but not [3H]glycine, release. The glycine-evoked release of [3H]D-ASP, but not that of [3H]GABA, and the GABA-evoked [3H]D-ASP release, but not that of [3H]glycine, were more pronounced in SOD1-G93A(+) than in SOD1(+) mice. Furthermore, these potentiations were already present in asymptomatic 30- to 40-day-old mice. Basal [3H]D-ASP release was also higher in SOD1-G93A(+) than SOD1(+) or SOD1(-)/G93A(-) mice. The release of endogenous glutamate and GABA was also enhanced in asymptomatic animals; the glycine-evoked release of endogenous glutamate, but not of endogenous GABA, was higher in SOD1-G93A(+) than in SOD1(+) animals. The effects of glycine and GABA were insensitive to receptor blockers, but sensitive to transporter inhibitors, indicating coexistence of glutamate and glycine transporters and of glutamate and GABA transporters on glutamate-releasing terminals. The glutamate release machinery seems excessively functional in SOD1-G93A(+) animals.
在肌萎缩侧索硬化症的转基因模型SOD1 - G93A(+)小鼠、SOD1(+)小鼠和SOD1(-)/G93A(-)动物中，研究了甘氨酸诱发的[3H]D - 天冬氨酸（[3H]D - ASP）或[3H]GABA的释放，以及GABA诱发的脊髓突触体中[3H]D - ASP或[3H]甘氨酸的释放。突变小鼠在病理晚期或症状前期被处死。在SOD1(-)/G93A(-)或SOD1(+)小鼠中，甘氨酸诱发[(3)H]d - ASP和[(3)H]GABA的释放，而GABA引起[3H]D - ASP的释放，但不引起[3H]甘氨酸的释放。与SOD1(+)小鼠相比，SOD1 - G93A(+)小鼠中甘氨酸诱发的[3H]D - ASP释放（而非[3H]GABA释放）以及GABA诱发的[3H]D - ASP释放（而非[3H]甘氨酸释放）更为明显。此外，这些增强作用在无症状的30至40日龄小鼠中就已存在。SOD1 - G93A(+)小鼠的基础[3H]D - ASP释放也高于SOD1(+)或SOD1(-)/G93A(-)小鼠。无症状动物中内源性谷氨酸和GABA的释放也增强；与SOD1(+)动物相比，SOD1 - G93A(+)小鼠中甘氨酸诱发的内源性谷氨酸释放（而非内源性GABA释放）更高。甘氨酸和GABA的作用对受体阻断剂不敏感，但对转运体抑制剂敏感，表明谷氨酸释放终末上存在谷氨酸和甘氨酸转运体以及谷氨酸和GABA转运体的共存。在SOD1 - G93A(+)动物中，谷氨酸释放机制似乎功能亢进。
