Rbm8a regulates neurogenesis and reduces Alzheimer's disease-associated pathology in the dentate gyrus of 5×FAD mice  

作　　者：Chenlu Zhu Xiao Ren Chen Liu Yawei Liu Yonggang Wang 

机构地区：[1]Department of Neurology,Lanzhou University Second Hospital [2]Department of Neurology,The First Affiliated Hospital of Nanchang University [3]Department of Neurology,Xiaogan City Central Hospital [4]Health Service Department of the Guard Bureau of the General Office of the Central Committee of the Communist Party of China [5]Headache Center,Department of Neurology,Beijing Tiantan Hospital,Capital Medical University

出　　处：《Neural Regeneration Research》2024年第4期863-871,共9页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.91849104(to YW)。

摘　　要：Alzheimer’s disease is a prevalent and debilitating neurodegenerative condition that profoundly affects a patient’s daily functioning with progressive cognitive decline,which can be partly attributed to impaired hippocampal neurogenesis.Neurogenesis in the hippocampal dentate gyrus is likely to persist throughout life but declines with aging,especially in Alzheimer’s disease.Recent evidence indicated that RNA-binding protein 8A(Rbm8a)promotes the proliferation of neural progenitor cells,with lower expression levels observed in Alzheimer’s disease patients compared with healthy people.This study investigated the hypothesis that Rbm8a overexpression may enhance neurogenesis by promoting the proliferation of neural progenitor cells to improve memory impairment in Alzheimer’s disease.Therefore,Rbm8a overexpression was induced in the dentate gyrus of 5×FAD mice to validate this hypothesis.Elevated Rbm8a levels in the dentate gyrus triggered neurogenesis and abated pathological phenotypes(such as plaque formation,gliosis reaction,and dystrophic neurites),leading to ameliorated memory performance in 5×FAD mice.RNA sequencing data further substantiated these findings,showing the enrichment of differentially expressed genes involved in biological processes including neurogenesis,cell proliferation,and amyloid protein formation.In conclusion,overexpressing Rbm8a in the dentate gyrus of 5×FAD mouse brains improved cognitive function by ameliorating amyloid-beta-associated pathological phenotypes and enhancing neurogenesis.

关 键 词：Adora2a Alzheimer’s disease ASTROCYTE cAMP signaling pathway dentate gyrus dystrophic neurites MICROGLIA NEUROGENESIS PLAQUE Rbm8a 

分 类 号：R749.16[医药卫生—神经病学与精神病学]