Department of Pharmacology and Toxicology and Metabolic Diseases Research Laboratory, School of Dentistry, Kyung Hee University, Seoul 130-701, Korea.
J Neural Transm (Vienna). 2010 Dec;117(12):1411-8. doi: 10.1007/s00702-010-0516-2. Epub 2010 Nov 11.
Diabetes has been associated with memory and behavioral dysfunctions such as anxiety. However, exact mechanisms of how diabetes affect such changes remain to be characterized. The purpose of present study is to search for streptozotocin-regulated genes in hippocampus of the mice using a differential display PCR technique, in the hope of type I diabetes-related hippocampal gene(s). It has been found that expression of a PCR product was increased by streptozotocin treatment and it was identified as β amyloid precursor protein. These results were further confirmed by performing RT-PCR analysis. In addition, the protein expression of β amyloid precursor protein as evidenced by Western blot analysis was increased in the hippocampus of streptozotocin-induced diabetic mice. To explore if the changes in amyloid β precursor protein could be related with functional changes in the brain regarding memory activity and anxiety, passive avoidance test and elevated plus maze test were performed, respectively. There is significant reduction of memory formation and marked induction of anxiety in the streptozotocin-induced diabetic mice. These results suggest that increase of β amyloid precursor protein may play a role in the memory loss and anxiety induction in type I diabetic mice.
糖尿病与记忆和行为功能障碍有关，如焦虑。然而，糖尿病如何影响这些变化的确切机制仍有待阐明。本研究的目的是使用差异显示 PCR 技术搜索链脲佐菌素调节的小鼠海马基因，以期找到与 1 型糖尿病相关的海马基因。研究发现，PCR 产物的表达因链脲佐菌素处理而增加，被鉴定为β淀粉样前体蛋白。通过进行 RT-PCR 分析进一步证实了这些结果。此外，Western blot 分析表明，β淀粉样前体蛋白的蛋白表达在链脲佐菌素诱导的糖尿病小鼠海马中增加。为了探讨β淀粉样前体蛋白的变化是否与大脑的记忆活动和焦虑的功能变化有关，分别进行了被动回避试验和高架十字迷宫试验。链脲佐菌素诱导的糖尿病小鼠的记忆形成显著减少，焦虑明显增加。这些结果表明，β淀粉样前体蛋白的增加可能在 1 型糖尿病小鼠的记忆丧失和焦虑诱导中起作用。
