咖啡因在帕金森病小鼠模型中神经保护作用的转录组学分析  

The neuroprotective effects of caffeine on the mice model of Parkinson’s disease:a transcriptomic analysis

作　　者：郑余银[1] 冯艺佳 阮青青[2] 屠文展[1] ZHENG Yuyin;FENG Yijia;RUAN Qingqing;TU Wenzhan(Department of Rehabilitation Medicine,the Second Affiliated Hospital of Wenzhou Medical University,Wenzhou 325027,China;Department of Neurology,the First Affiliated Hospital of Wenzhou Medical University,Wenzhou 325015,China)

机构地区：[1]温州医科大学附属第二医院康复医学科,浙江温州325027 [2]温州医科大学附属第一医院神经内科,浙江温州325015

出　　处：《温州医科大学学报》2021年第6期444-448,453,共6页Journal of Wenzhou Medical University

基　　金：浙江省医药卫生科技计划项目(2017KY482);浙江省医药卫生科技计划骨干人才项目(2014RCA018)。

摘　　要：目的:通过转录组学分析探讨咖啡因对帕金森病认知功能(工作记忆)保护作用的可能分子机制。方法:采取脑立体定位注射的方式,在小鼠双侧海马脑区注射α-突触核蛋白(α-Syn)纤维体并给予咖啡因喂养。3个月后取小鼠海马组织进行转录组测序(RNA-seq)分析。结果:α-Syn在海马脑区明显聚集且小鼠表现出工作记忆能力受损(P<0.05);咖啡因可有效改善α-Syn诱导的小鼠认知障碍(P<0.05);α-Syn造模后的转录组变化主要富集在小胶质细胞激活及趋化招募等信号通路;而长期饮用咖啡因可显著增强细胞的增殖能力(P<0.05)。结论:咖啡因可能是通过促进细胞增殖来修复α-Syn引起的神经炎症损伤。Objective:To investigate by transcriptomics the possible molecular mechanism of the protective effect of caffeine in Parkinson’s disease,so as to provide new evidence for elucidating the neuroprotective effect of caffeine.Methods:The mice were injected withα-synuclein(α-Syn)fibril in the hippocampal region by stereotaxic injection,and were fed with caffeine.Three months later,the hippocampus tissues were isolated for transcriptome sequencing(RNA-seq).Results:α-synuclein was obviously aggregated in hippocampus and impaired the working memory in mice(P<0.05).Long-term drinking caffeine could effectively improve the cognitive impairment caused byα-Synuclein in mice(P<0.05).The transcriptome changes induced byα-Synuclein were mainly enriched in the pathways of microglial activation and chemokines signaling.Chronic caffeine consumption significantly improved the cell proliferation(P<0.05).Conclusion:Caffeine may repair the neuronal inflammatory damage caused byα-Syn via promoting cell proliferation.

关 键 词：帕金森病 Α-突触核蛋白 认知障碍 转录组学 

分 类 号：R741[医药卫生—神经病学与精神病学]