PSD-95基因DNA甲基化在睡眠剥夺相关疾病的作用研究进展  

Research progress on the role of PSD-95 gene DNA methylation modification in sleep deprivation related diseases

作　　者：马江磊 张慧杰 王光明 MA Jianglei;ZHANG Huijie;WANG Guangming(School of Clinical Medicine,Dali University,Dali 671000,Yunnan,China;Department of Obstetrics,Yantai Yuhuangding Hospital,Yantai 264000,Shandong,China;Center of Genetic Testing,the First Hospital of Dali University,Dali 671000,Yunnan,China)

机构地区：[1]大理大学临床医学院,云南大理671000 [2]烟台毓璜顶医院产科,山东烟台264000 [3]大理大学第一附属医院基因检测中心,云南大理671000

出　　处：《右江医学》2024年第1期6-11,共6页Chinese Youjiang Medical Journal

基　　金：国家自然科学基金(82160244);云南省卫生计生委医学学科带头人项目(D-2017057);云南省教育厅科学研究基金项目(2023Y0989)。

摘　　要：睡眠剥夺(SD)已成为世界各地普遍存在的问题,许多疾病的发生与睡眠不足有关。已经发现表观遗传机制与SD及相关疾病的发生发展密切相关,其中,DNA甲基化是最常见的表观遗传修饰,可影响基因表达。突触后密度蛋白-95(PSD-95)被认为是兴奋性信号传递过程中重要的调节因子,SD后,PSD-95表达降低,表现出情绪改变和认知障碍等精神疾病症状。在慢性应激小鼠中,观察到血清素1A受体启动子区DNA甲基化水平增加,与抑郁症患者前额叶皮层PSD-95表达水平降低有关。然而,PSD-95基因的DNA甲基化水平与抑郁症表型无关。在精神分裂症患者中,SD的长度会加重疾病程度,且PSD-95基因DNA甲基化与精神分裂症有关。此外,结直肠癌的发病风险与SD或昼夜节律紊乱有关,而PSD-95基因DNA甲基化也可能成为治疗结直肠肿瘤的靶点。未来仍需要进一步深入探索PSD-95基因DNA甲基化在SD相关疾病中的作用及调节机制。Sleep deprivation(SD)is a widespread problem worldwide and is associated with various diseases.It has been found that the epigenetic mechanism is closely related to the occurrence and development of SD and related diseases,among which DNA methylation is the most common epigenetic modification that can affect gene expression.Postsynaptic density protein-95(PSD-95)is considered an important regulatory factor in the process of excitatory signaling.After SD,the expression of PSD-95 decreases,exhibiting symptoms of mental illness such as emotional changes and cognitive impairment.In chronic stress mice,an increase in DNA methylation levels in the promoter region of serotonin 1A receptor is observed,which is associated with a decrease in PSD-95 expression levels in the prefrontal cortex of patients with depression.However,the DNA methylation level of the PSD-95 gene is not associated with the phenotype of depression.In patients with schizophrenia,the length of SD can exacerbate the severity of the disease,and DNA methylation of the PSD-95 gene is associated with schizophrenia.In addition,the risk of colorectal cancer is associated with SD or circadian rhythm disorders,and DNA methylation of the PSD-95 gene may also become a target for the treatment of colorectal tumors.Further researches are needed to explore the role and regulatory mechanism of DNA methylation of the PSD-95 gene in SD-related diseases.

关 键 词：睡眠剥夺 突触后密度蛋白-95 DNA甲基化 表观遗传 

分 类 号：R749.1[医药卫生—神经病学与精神病学]