异相睡眠剥夺对大鼠学习记忆能力及海马基因表达谱的影响

摘要

目的 观察96 h异相睡眠剥夺(PSD)对大鼠学习记忆能力及海马基因表达谱的影响.方法 利用改良多平台水环境法制备PSD动物模型,六角迷宫行为学范式评价大鼠学习记忆能力;在此基础上利用基因芯片技术研究PSD对大鼠海马全集因表达谱的影响,对差异基因(上调或者下调倍数变化值≥2.0,且P值≤0.05)进行GO和KEGG富集分析;并对部分差异表达基因进行RT-PCR验证.结果 与大平台对照组(TC)比较,PSD大鼠认知率明显降低(P<0.05);两组大鼠海马差异表达基因共100个:其中25个基因上调,75个基因下调;GO分析结果表明,上调基因主要与细胞生长及分化的负性调节、学习记忆、炎症反应、氧化应激、突触传递等生物学过程有关;下调基因主要与免疫应答、神经系统发育、突触传递、代谢过程、信号转导、递质分泌、细胞凋亡、转录过程等过程有关;利用KEGG数据库对差异基因进行信号通路分析,发现差异基因主要参与cGMP-PKG、代谢、NF-κB、癌症等多条信号通路过程.结论 PSD可引起大鼠记忆能力的下降,并伴随海马多种基因表达异常;PSD 导致的学习记忆能力下降可能与多种基因表达及信号通路的变化有关.%Aim To investigate the effect of 96 h paradoxical sleep deprivation(PSD) on learning & memory ability of rats and the concomitant gene expression change in the rat hippocampus.Methods PSD model was established by Modified Multiple Platform Method(MMPM).Learning and memory ability of the PSD model was assessed through hexagonal maze compared with the control, and the gene expression in hippocampus of each group was detected by gene chip technology.After that, GO and KEGG enrichment analysis were applied to determine the changes of the gene expression in PSD model compared with the control.Results PSD affected the memory consolidation process in rats.The gene chips showed that 100 genes expressed differently in the hippocampus of PSD model compared with the control, and among them, 25 genes were up-regulated and 75 genes down-regulated.The up-regulated genes mainly involved in cell growth and differentiation, learning and memory, inflammation, oxidative stress, and biological processes such as synaptic transmission, while the down-regulated genes mainly involved in immune response, central nervous system development, synaptic transmission, metabolism, signal transduction, neurotransmitter secretion, cell apoptosis, and so on.KEGG analysis showed that genes differentially expressed mainly involved in cGMP-PKG, metabolism, NF-kappa B and Pathways in cancer, and so on.Conclusion In rats, PSD leads to memory deficit, as well as a variety of gene expression changes in hippocampus of the PSD model.