Forskolin调节DHA对APP/PS1转基因小鼠突触可塑性和认知功能的增强作用

Forskolin regulates the enhancing effects of DHA on the synaptic plasticity and cognitive function in APP/PS1 transgenic mice

目的研究Forskolin调节DHA对APP/PS1转基因小鼠突触可塑性和认知功能的影响。方法对7月龄APP/PS1小鼠给予DHA及DHA和forskolin联合进行治疗。30d后,通过行为学试验检测其认知功能;通过组织病理学试验检测脑内细胞密度及脑突触形成能力和突触标记物Synaptophysin的表达以及通过Western blotting检测脑内pCREB1蛋白含量。结果 8月龄APP/PS1小鼠海马区面积、细胞密度、Synaptophysin和脑内pCREB1蛋白均明显降低,行为学上出现了明显的认知功能障碍。单独给予DHA以及DHA和forskolin联合给药治疗后,APP/PS1小鼠海马区面积、细胞密度、Synaptophysin和脑内pCREB1蛋白均增加,认知功能障碍得到改善,并且联合给药组的效果更为显著,但是均未恢复至生理水平。结论 DHA和forskolin联合治疗后,forskolin增强DHA对APP/PS1转基因小鼠突触病理和认知障碍的治疗作用。

Objective To investigate if Forskolin regulates the enhancing effects of DHA on the synaptic plasticity and cognitive function in APP/PS1 transgenic mice. Methods 7-month old APP/PS1 mice were treated with DHA ＋ forskolin or DHA alone. 30 days later, cognitive function was detected by behavioral test; the expression of Synaptophysin, synapse formation ability, ceils density were detected by histopathological test and intracerebral pCREB1 protein burden was evaluated by Western blotting. Results The area of hippocampus, cell density, Synaptophysin and intracerebral pCREB1 protein levels were significantly decreased in 8-month old APP/PS1 mice, with a significant cognitive impairment in the behavior compared to normal control, but increased after administration of DHA alone or DHA＋ forskolin, with cognitive dysfunction improvement and better in DHA＋ forskolin than in DHA alone, but not restored to the normal control. Conclusion Forskolin could enhance the therapeutic effects of DHA on cognitive function and synaptic plasticity through the combined treatment of DHA and forskolin in AD transgenic mice.