丁酸钠通过维持乙酰化平衡改善帕金森病模型鼠认知功能和情感障碍

Sodium butyrate improved cognitive and affective disorder of PD model mice mainly via maintenance of histone acetylation homeostasis

目的研究丁酸钠对帕金森病(Parkinson’s disease,PD)模型小鼠认知功能和情感障碍影响及机制。方法C57BL/6J鼠随机分为对照组、MPTP组、丁酸钠组、MPTP+丁酸钠组,通过悬尾实验和Morris水迷宫实验研究丁酸钠对PD模型鼠认知功能和情感障碍的影响;Western blot和RT-PCR检测酪氨酸羟化酶(tyrosine hydroxylase,TH)和组蛋白去乙酰化酶1(histone deacetylase 1,HDAC1)蛋白表达和mRNA水平。结果与对照组比较,PD模型鼠表现为学习记忆能力下降和抑郁样行为;丁酸钠能够改善PD模型鼠抑郁行为,并明显提高PD模型鼠学习记忆能力;丁酸钠可使PD模型鼠脑组织TH和HDAC1蛋白表达和mRNA水平明显升高。结论 MPTP诱导TH蛋白表达明显降低,引起PD模型鼠认知和情感障碍,可能是干扰了组蛋白乙酰化平衡;丁酸钠能够使PD模型鼠脑组织TH表达明显升高,改善PD模型鼠认知功能和情感障碍,主要是通过保护多巴胺神经元、修复和维持组蛋白乙酰化和去乙酰化动态平衡来完成的。

Aim To explore the effects of sodium butyrate on cognitive and affective disorder in Parkinson’s disease（PD） model mice.Methods C57BL/6J mice were impaired by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine（MPTP） and mice were randomly assigned into four groups,namely,control group,MPTP group,sodium butyrate group and MPTP plus sodium butyrate group.The cognitive and affective functions were observed using Morris Water Maze test and tail suspension test.The protein and mRNA levels of TH and HDAC1 were detected by Western blot and RT-PCR methods.Results MPTP decreased the ability of learning and memory and caused depression-like behavior;sodium butyrate could significantly improve the depressive behavior and enhance the ability of learning and memory in PD model mice.The protein expression and mRNA levels of TH and HDAC1 were significantly increased after sodium butyrate treatment in PD model mice.Conclusion MPTP decreased the expression of TH,and induced cognitive and affective disorder,which may interfere with the homeostasis of histone acetylation;sodium butyrate could increase TH protein expression and improve cognitive and affective disorder of PD model mice.The mechanism may be through protecting dopamine neurons and maintaining the homeostasis of histone acetylation and deacetylation.