Zhong Yuan, Zhu Yitong, He Ting, Li Wei, Yan Hong, Miao Ya
Department of Geriatrics, Shanghai Jiao Tong University affiliated Sixth People's Hospital, 600 Yi Shan Road, Shanghai 200233, China.
Department of Boxi medical center, The First Affiliated Hospital of Soochow University, No. 188 Shizi St, Suzhou, Jiangsu 215006, China.
Neurosci Lett. 2016 Jan 1;610:171-6. doi: 10.1016/j.neulet.2015.09.023. Epub 2015 Nov 10.
Diabetics suffer from a higher risk of cognitive decline. cAMP response element-binding protein (CREB) is a transcription factor associated with memory and synaptic plasticity. Here, we investigated the molecular changes in the hippocampus correlated with diabetes associated cognitive decline (DACD) from a CREB-centered perspective in a rat model of type 2 diabetes. Furthermore, we tested the therapeutic effect of rolipram on DACD. High-fat diet and low-dose streptozocin were adopted to induce diabetes in SD rats. Results show that supplementation with rolipram for 23 days (0.5mg/kg, once a day) improved the performance of diabetic rats in Morris water navigation task with increased level of CREB, brain-derived neurotrophic factor (BDNF), and Arc protein in the hippocampus. Rolipram, acting as an inhibitor of PDE4, was found to repair the imbalance in the CREB/BDNF/Arc pathway. This study may provide important insights into the mechanisms underlying DACD and provide new therapeutic targets for clinical treatment.
糖尿病患者认知功能下降的风险更高。环磷酸腺苷反应元件结合蛋白（CREB）是一种与记忆和突触可塑性相关的转录因子。在此，我们以CREB为中心，在2型糖尿病大鼠模型中研究了与糖尿病相关认知功能下降（DACD）相关的海马分子变化。此外，我们测试了咯利普兰对DACD的治疗效果。采用高脂饮食和低剂量链脲佐菌素诱导SD大鼠患糖尿病。结果显示，连续23天补充咯利普兰（0.5mg/kg，每天一次）可改善糖尿病大鼠在莫里斯水迷宫任务中的表现，同时海马中CREB、脑源性神经营养因子（BDNF）和Arc蛋白水平升高。咯利普兰作为磷酸二酯酶4（PDE4）的抑制剂，可修复CREB/BDNF/Arc通路的失衡。本研究可能为DACD的潜在机制提供重要见解，并为临床治疗提供新的治疗靶点。
