Centre of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal.
Brain Res. 2011 Apr 6;1383:257-69. doi: 10.1016/j.brainres.2011.01.071. Epub 2011 Jan 28.
Diabetes induces changes in neurotransmitter release in central nervous system, which depend on the type of neurotransmitter and region studied. In this study, we evaluated the effect of diabetes (two and eight weeks duration) on basal and evoked release of [(14)C]glutamate and [(3)H]GABA in hippocampal and retinal synaptosomes. We also analyzed the effect of diabetes on the protein content of vesicular glutamate and GABA transporters, VGluT-1, VGluT-2 and VGAT, and on the α(1A) subunit of P/Q type calcium channels, which are abundant in nerve terminals. The protein content of vesicular glutamate and GABA transporters, and of the α(1A) subunit, was differently affected by diabetes in hippocampal and retinal synaptosomes. The changes were more pronounced in the retina than in hippocampus. VGluT-1 and VGluT-2 content was not affected in hippocampus. Moreover, changes occurred early, at two weeks of diabetes, but after eight weeks almost no changes were detected, with the exception of VGAT in the retina. Regarding neurotransmitter release, no major changes were detected. After two weeks of diabetes, neurotransmitter release was similar to controls. After eight weeks of diabetes, the basal release of glutamate slightly increased in hippocampus and the evoked GABA release decreased in retina. In conclusion, diabetes induces early transient changes in the content of glutamate and/or GABA vesicular transporters, and on calcium channels subunit, in retinal or hippocampal synaptosomes, but only minor changes in the release of glutamate or GABA. These results point to the importance of diabetes-induced changes in neural tissues at the presynaptic level, which may underlie alterations in synaptic transmission, particularly if they become permanent during the later stages of the disease.
糖尿病会引起中枢神经系统神经递质释放的变化，具体变化取决于所研究的神经递质类型和区域。在这项研究中，我们评估了糖尿病（持续 2 周和 8 周）对海马和视网膜突触体中[(14)C]谷氨酸和[(3)H]GABA 基础和诱发释放的影响。我们还分析了糖尿病对囊泡谷氨酸和 GABA 转运体、VGluT-1、VGluT-2 和 VGAT 以及神经末梢丰富的 P/Q 型钙通道α(1A)亚基的蛋白含量的影响。囊泡谷氨酸和 GABA 转运体以及α(1A)亚基的蛋白含量受糖尿病影响在海马和视网膜突触体中存在差异。这种变化在视网膜中比在海马中更为明显。在海马体中，VGluT-1 和 VGluT-2 的含量不受影响。此外，这些变化发生得很早，在糖尿病的第 2 周就出现了，但在第 8 周后几乎没有变化，除了视网膜中的 VGAT。至于神经递质释放，没有发现重大变化。糖尿病 2 周后，神经递质释放与对照组相似。糖尿病 8 周后，海马体中谷氨酸的基础释放略有增加，视网膜中 GABA 的诱发释放减少。总之，糖尿病会导致视网膜或海马突触体中谷氨酸和/或 GABA 囊泡转运体以及钙通道亚基的早期短暂变化，但谷氨酸或 GABA 的释放仅发生微小变化。这些结果表明，糖尿病引起的神经组织在突触前水平的变化可能是突触传递改变的基础，尤其是如果这些变化在疾病的后期变得永久的话。
