LncRNA NPTN-IT1-201 Ameliorates Depressive-like Behavior by Targeting miR-142-5p and Regulating Inflammation and Apoptosis via BDNF  

作　　者：Jun HE Peng XIE Xiao-qiong AN Dong-fen GUO Bin BI Gang WU Wen-feng YU Zhen-kui REN Li ZUO 

机构地区：[1]Department of Immunology,School of Basic Medical Science,Guizhou Medical University,Guiyang,550004,China [2]Department of Laboratory Medicine,The Second People’s Hospital of Guizhou Province,Guiyang,550004,China [3]Guizhou Provincial Center for Clinical Laboratory,Guiyang,550002,China [4]Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education,School of Basic Medical Science,Guizhou Medical University,Guiyang,550004,China [5]Psychosomatic Department,The Second People’s Hospital of Guizhou Province,Guiyang,550004,China

出　　处：《Current Medical Science》2024年第5期971-986,共16页当代医学科学（英文）

基　　金：supported by grants from the National Natural Science Foundation of China(No.82160311,No.82160225 and No.82060232);the Science and Technology Fund Project of Guizhou Health and Health Commission(No.gzwkj2021-356);Basic Science Technology Project of Guizhou Province[No.ZK(2021)412];the Special Project of Academic New Seedling Cultivation and Free Exploration Innovation-Post-project subsidy of the National Natural Science Foundation of China,“Thousand Levels”of Guizhou Province High Level Innovative Talents(No.gzwjrs 2023-012).

摘　　要：Objective Long noncoding RNAs(lncRNAs)and microRNAs(miRNAs)are widely expressed in the brain and are associated with the development of neurological and neurodegenerative diseases.However,their roles and molecular mechanisms in major depressive disorder(MDD)remain largely unknown.This study aimed to identify lncRNAs and miRNAs involved in the development of MDD and elucidate their molecular mechanisms.Methods Transcriptome and bioinformatic analyses were performed to identify miRNAs and lncRNAs related to MDD.C57 mice were subjected to chronic unpredictable mild stress(CUMS)to establish a depression model.Lentiviruses containing either lncRNA NPTN-IT1-201 or miR-142-5p were microinjected into the hippocampal region of these mice.Behavioral tests including the sucrose preference test(SPT),tail suspension test(TST),and forced swim test(FST)were conducted to evaluate depressive-like behaviors.Results The results revealed that overexpression of lncRNA NPTN-IT1-201 or inhibition of miR-142-5p significantly ameliorated depressive-like behaviors in CUMS-treated mice.Dual-luciferase reporter assays confirmed interactions between miR-142-5p with both brain-derived neurotrophic factor(BDNF)and NPTN-IT1-201.ELISA analysis revealed significant alterations in relevant biomarkers in the blood samples of MDD patients compared to healthy controls.Histological analyses,including HE and Nissl staining,showed marked structural changes in brain tissues following CUMS treatment,which were partially reversed by lncRNA NPTN-IT1-201 overexpression or miR-142-5p inhibition.Immunofluorescence imaging demonstrated significant differences in the levels of BAX,Bcl2,p65,Iba1 among different treatment groups.TUNEL assays confirmed reduced apoptosis in brain tissues following these interventions.Western blotting showed the significant differences in BDNF,BAX,and Bcl2 protein levels among different treatment groups.Conclusion NPTN-IT1-201 regulates inflammation and apoptosis in MDD by targeting BDNF via miR-142-5p,making it a potential therapeut

关 键 词：depressive-like behavior chronic unpredictable mild stress long noncoding RNA microRNA brain-derived neurotrophic factor 

分 类 号：R749.4[医药卫生—神经病学与精神病学]