MBD5 regulates NMDA receptor expression and seizures by inhibiting Stat1 transcription

作者全名："Tang, Feng-lin; Zhang, Xiao-gang; Ke, Ping-yang; Liu, Jie; Zhang, Zhi-juan; Hu, Dan-mei; Gu, Juan; Zhang, Hui; Guo, Hao-kun; Zang, Qian-wen; Huang, Rui; Ma, Yuan-lin; Kwan, Patrick"

作者地址："[Tang, Feng-lin; Zhang, Xiao-gang; Ke, Ping-yang; Liu, Jie; Zhang, Zhi-juan; Gu, Juan; Zhang, Hui; Guo, Hao-kun; Huang, Rui; Ma, Yuan-lin; Kwan, Patrick] Chongqing Med Univ, Dept Neurol, Chongqing Key Lab Neurol, Affiliated Hosp 1, Chongqing 400016, Peoples R China; [Kwan, Patrick] Monash Univ, Cent Clin Sch, Dept Neurosci, Melbourne, Australia; [Zhang, Xiao-gang] Chongqing Gen Hosp, Dept Neurol, Chongqing Key Lab Neurodegenerat Dis, Chongqing 401147, Peoples R China; [Hu, Dan-mei] Shanxi Med Univ, Shanxi Bethune Hosp, Tongji Shanxi Hosp, Shanxi Acad Med Sci,Hosp 3,Dept Neurol, Taiyuan 030032, Peoples R China; [Hu, Dan-mei] Shanxi Med Univ, Key Lab Cellular Physiol, Minist Educ, Taiyuan, Peoples R China; [Zang, Qian-wen] Chongqing Med Univ, Affiliated Hosp 2, Dept Rehabil Med & Phys Therapy, Chongqing, Peoples R China; [Kwan, Patrick] Alfred Ctr, Level 6,99 Commercial Rd, Melbourne, Vic 3004, Australia"

通信作者："Kwan, P (通讯作者)，Alfred Ctr, Level 6,99 Commercial Rd, Melbourne, Vic 3004, Australia."

来源：NEUROBIOLOGY OF DISEASE

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:000976836200001

JCR分区：Q1

影响因子：5.1

年份：2023

卷号：181

期号：　

开始页：　

结束页：　

文献类型：Article

关键词：MBD5; Neuroscience; Epilepsy

摘要："Epilepsy is considered to result from an imbalance between excitation and inhibition of the central nervous system. Pathogenic mutations in the methyl-CpG binding domain protein 5 gene (MBD5) are known to cause epilepsy. However, the function and mechanism of MBD5 in epilepsy remain elusive. Here, we found that MBD5 was mainly localized in the pyramidal cells and granular cells of mouse hippocampus, and its expression was increased in the brain tissues of mouse models of epilepsy. Exogenous overexpression of MBD5 inhibited the transcription of the signal transducer and activator of transcription 1 gene (Stat1), resulting in increased expression of N-methyl-D-aspartate receptor (NMDAR) subunit 1 (GluN1), 2A (GluN2A) and 2B (GluN2B), leading to aggravation of the epileptic behaviour phenotype in mice. The epileptic behavioural phenotype was alleviated by overexpression of STAT1 which reduced the expression of NMDARs, and by the NMDAR antagonist memantine. These results indicate that MBD5 accumulation affects seizures through STAT1-mediated inhibition of NMDAR expression in mice. Collectively, our findings suggest that the MBD5-STAT1-NMDAR pathway may be a new pathway that regulates the epileptic behavioural phenotype and may represent a new treatment target."

基金机构："National Natural Science Foundation of China [81901322, 82271497]"

基金资助正文：This work was supported by the National Natural Science Foundation of China (81901322 and 82271497).