Center of Ophthalmology and Vision Sciences, IBILI, Faculty of Medicine, University of Coimbra, 3004-548 Coimbra, Portugal.
Neuroscience. 2010 Sep 15;169(4):1589-600. doi: 10.1016/j.neuroscience.2010.06.021. Epub 2010 Jun 19.
Diabetes has been associated with cognitive and memory impairments, and with alterations in color and contrast perception, suggesting that hippocampus and retina are particularly affected by this disease. A few studies have shown that diabetes differentially affects neurotransmitter release in different brain regions and in retina, and induces structural and molecular changes in nerve terminals in both hippocampus and retina. We now detailed the impact over time of diabetes (2, 4 and 8 weeks of diabetes) on a large array of exocytotic proteins in hippocampus and retina.The exocytotic proteins density was evaluated by immunoblotting in purified synaptosomes and in total extracts of hippocampus and retina from streptozotocin-induced diabetic and age-matched control animals. Diabetes affected differentially the content of synaptic proteins (VAMP-2, SNAP-25, syntaxin-1, synapsin-1 and synaptophysin) in hippocampal and retinal nerve terminals. Changes were more pronounced and persistent in hippocampal nerve terminals. In general, the alterations in retina occurred earlier, but were transitory, with the exception of synapsin-1, since its content decreased at all time points studied. The content of synaptotagmin-1 and rabphilin 3a in nerve terminals of both tissues was not affected. In total extracts, no changes were detected in the retina, whereas in hippocampus SNAP-25 and syntaxin-1 content was decreased, particularly when more drastic changes were also detected in nerve terminals. These results show that diabetes affects the content of several exocytotic proteins in hippocampus and retina, mainly at the presynaptic level, but hippocampus appears to be more severely affected. These changes might influence neurotransmission in both tissues and may underlie, at least partially, previously detected physiological changes in diabetic humans and animal models. Since diabetes differentially affects exocytotic proteins, according to tissue and insult duration, functional studies will be required to assess the physiological impairment induced by diabetes on the exocytosis in central synapses.
糖尿病与认知和记忆障碍有关，并且与颜色和对比感知的改变有关，这表明海马体和视网膜特别容易受到这种疾病的影响。一些研究表明，糖尿病在不同的脑区和视网膜中对神经递质的释放有不同的影响，并在海马体和视网膜的神经末梢诱导结构和分子变化。我们现在详细描述了糖尿病（糖尿病 2、4 和 8 周）对海马体和视网膜中大量外排蛋白的长期影响。通过免疫印迹法在纯化的突触小体和来自链脲佐菌素诱导的糖尿病和年龄匹配的对照动物的海马体和视网膜的总提取物中评估外排蛋白的密度。糖尿病以不同的方式影响海马体和视网膜神经末梢突触蛋白（VAMP-2、SNAP-25、突触素-1、突触素-1 和突触小体蛋白）的含量。在海马体神经末梢中，变化更为明显且持久。一般来说，视网膜中的变化发生得更早，但都是暂时的，除了突触素-1，因为它的含量在所有研究的时间点都下降了。两种组织神经末梢的突触结合蛋白-1 和 rabphilin 3a 的含量没有变化。在总提取物中，视网膜没有变化，而在海马体中，SNAP-25 和突触素-1 的含量减少，尤其是当神经末梢也检测到更剧烈的变化时。这些结果表明，糖尿病影响海马体和视网膜中外排蛋白的含量，主要是在突触前水平，但海马体似乎受到更严重的影响。这些变化可能会影响两种组织中的神经传递，并且可能至少部分解释了以前在糖尿病患者和动物模型中检测到的生理变化。由于糖尿病根据组织和损伤持续时间对外排蛋白的影响不同，因此需要进行功能研究来评估糖尿病对中枢突触外排的生理损伤。
