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

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

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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 Bc12 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 therapeutic target for MDD.

depressive-like behaviorchronic unpredictable mild stresslong noncoding RNAmicroRNAbrain-derived neurotrophic factor

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

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Department of Immunology,School of Basic Medical Science,Guizhou Medical University,Guiyang 550004,China

Department of Laboratory Medicine,The Second People's Hospital of Guizhou Province,Guiyang 550004,China

Guizhou Provincial Center for Clinical Laboratory,Guiyang 550002,China

Key Laboratory of Endemic and Ethnic Diseases,Ministry of Education,School of Basic Medical Science,Guizhou Medical University,Guiyang 550004,China

Psychosomatic Department,The Second People's Hospital of Guizhou Province,Guiyang 550004,China

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2024

10.1007/s11596-024-2917-8

当代医学科学(英文)
华中科技大学同济医学院

当代医学科学(英文)

影响因子：0.748
ISSN：2096-5230
年,卷(期)：2024.44(5)