Targeted Delivery of Engineered RVG-BDNF-Exosomes:A Novel Neurobiological Approach for Ameliorating Depression and Regulating Neurogenesis  

作　　者：Shaobo Liu Lei Chen Mei Guo Yongbiao Li Qingshan Liu Yong Cheng 

机构地区：[1]Key Laboratory of Ethnomedicine for Ministry of Education,Center on Translational Neuroscience,Minzu University of China,Beijing 100081,China [2]College of Life and Environmental Sciences,Minzu University of China,Beijing 100081,China [3]Institute of National Security,Minzu University of China,Beijing 100081,China

出　　处：《Research》2025年第1期534-548,共15页研究(英文)

基　　金：supported by the National Natural Science Foundation of China(no.82071676).

摘　　要：Addressing the urgent need for innovative depression treatments,this study heralds a breakthrough in major depressive disorder(MDD)therapy by intertwining clinical observations with neurobiological advancements.We analyzed brain-derived neurotrophic factor(BDNF)levels in serum exosomes from a diverse group of 60 individuals,including first-episode,drug-free MDD patients,medicated MDD patients,and healthy controls.Our results revealed a significant decrease in BDNF levels within MDD patients’exosomes,which notably increased post-medication,highlighting BDNF’s potential as a biomarker for both MDD diagnosis and treatment efficacy.Advancing these clinical findings,we developed RVG-modified exosomes engineered to overexpress BDNF(RVG-BDNF-Exos),designed to directly target neuronal cells.Our findings demonstrate that these engineered exosomes can successfully traverse the blood–brain barrier,targeting neurons in the hippocampus and prefrontal cortex.In our mouse model of depression induced by lipopolysaccharide,RVG-BDNF-Exos treatment led to a significant increase of BDNF in these key brain regions,crucial for mood regulation and neurogenesis.This intervention modulated the BDNF/TrkB/AKT signaling pathway,central to neural plasticity and implicated in depression’s pathogenesis.Behavioral assessments exhibited substantial improvements in depressive-like behaviors in mice treated with RVG-BDNF-Exos,including reduced immobility in Tail Suspension and Forced Swim Tests.Additionally,our treatment effectively decreased neuroinflammation,as evidenced by the reduction in microglia and astrocyte numbers.Moreover,RVG-BDNF-Exos treatment enhanced neurogenesis and regulated synaptic plasticity,as indicated by the increased expression of neuronal markers MAP2 and DCX,and synaptic proteins PSD95 and Syn-1.In conclusion,this study not only underscores the clinical potential of serum exosomal BDNF as a diagnostic and therapeutic marker for MDD but also demonstrates the efficacy of RVG-BDNF-Exos in alleviating depressive sympt

关 键 词：blood brain barrier major depressive disorder mdd therapy RVG BDNF exosomes depression therapy serum exosomes engineered exosomes targeted delivery NEUROGENESIS 

分 类 号：R749.4[医药卫生—神经病学与精神病学]