Increased expression of β amyloid precursor gene in the hippocampus of streptozotocin-induced diabetic mice with memory deficit and anxiety induction

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 beta amyloid precursor protein. These results were further confirmed by performing RT-PCR analysis. In addition, the protein expression of beta 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 beta 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 beta amyloid precursor protein may play a role in the memory loss and anxiety induction in type I diabetic mice.