小膠質(zhì)細胞在抑郁癥發(fā)病機制中的作用

約有5%的人口患有MDD[1],給社會帶來了巨大的疾病負擔(dān)和挑戰(zhàn)。MDD不僅嚴(yán)重D的復(fù)雜性和異質(zhì)性使得其病因和病理生理機制至今尚不清晰。MDD被視為是一模型中進一步發(fā)現(xiàn)小膠質(zhì)細胞的激活與抑郁樣行為的出現(xiàn)有關(guān)[7]。與此同時，抗抑郁藥物已被證實能夠有效緩解小膠質(zhì)細胞的異常激活[膠質(zhì)細胞和MDD之間關(guān)聯(lián)的相關(guān)文獻。文獻檢索時間為主要為2013—2023年，檢索時使用英文關(guān)鍵詞“microglial”and“depressionordepressivedisorder”,中文關(guān)鍵詞“小膠質(zhì)細胞”和“抑郁癥或抑郁障礙”及運用布爾邏輯深度，以形成一個綜合性的研究基礎(chǔ)。通過以上檢索方式獻10篇，近五年文獻數(shù)量占比82%。本研究運用定性二、小膠質(zhì)細胞的功能而M2極化表型則表現(xiàn)出更為復(fù)雜的功能多樣性，這些細胞不僅參與細胞碎片的簡單的二元劃分可能無法充分捕捉到小膠質(zhì)細胞在實際生物環(huán)境中所展現(xiàn)功能衍生的集落刺激因子1(colonystimulatingfactor1,CSF1)可阻斷小膠質(zhì)細作用[14-15],在慢性不可預(yù)知溫和應(yīng)激(chronicunpredictablemildstress,B,NF-kB)信號通路抑制小膠質(zhì)細胞的活化，從而緩解炎性反應(yīng)達到抗抑郁作用NA表達水平顯著增加，這些變化在CUS暴露結(jié)束后仍持續(xù)時間長達6周。有趣的n-likegrowthfactor-2,IGF2),在脂多糖(lipopolysaccharide,L過介導(dǎo)小膠質(zhì)細胞中的細胞外信號調(diào)節(jié)激酶-神經(jīng)生長因子結(jié)合蛋白1-cAMP反NF的水平，進而降低促炎細胞因子的釋放或平衡犬尿氨損傷[32-33]。使用集落刺激因子1受體拮抗劑PLX5622誘導(dǎo)全腦小膠質(zhì)細胞衰cialdefeatstress,CSDS)小鼠的研究中，觀察到離子化鈣結(jié)合適配分ombinantionizedcalci興奮性突觸的吞噬作用，而非抑制性突觸的吞噬[OD樣受體熱蛋白結(jié)構(gòu)域相關(guān)蛋白3(nod-likereceptorthermalproteindomalusterofdifferentiatio基質(zhì)和中間細胞的間接通訊和高效的直接膜-膜通訊形式的物理接觸[47],這些的直接通信依賴于小膠質(zhì)細胞表面的P2Y11可能通過直接靶向?qū)ι窠?jīng)系統(tǒng)的發(fā)育和再生具有重要作用，排斥性引導(dǎo)分子ap通過靶向抑制Kruppel樣因子4的基因，從而抑制神經(jīng)發(fā)生以及減少興奮性神和激活轉(zhuǎn)錄因子3(STAT3)敲除的慢性約束應(yīng)激小鼠在行為學(xué)實驗中表現(xiàn)出良好落刺激因子所介導(dǎo)的突觸活動調(diào)節(jié)抑郁行為[46]。[1]HerrmanH,PatelV,KielingCession:aLancet-WorldPsychiatricAssociationCommission[J].Lancet,2022,399(10328):957-1022.DOI:10.1016/S0140-6736(21)disorder:beyondmonoaminehypothesis[J].Ps[3]TarttAN,MarianiMB,HenR,etal.Dysregulationofadulthippocaimplications[J].MolPsychiatry,2022,27(6):2689-2699.DOI:10.103[J].SciChinaLifeScoleinthebrain[J].MolPsychiatry,2020,25(2):351-367.D/JNEUROSCI.0184-19.2019.elinganddepressive-likeb-49.DOI:10.1016/j.biopsych.2017.05.026.[8]MarianiN,EversonJ,ParianteCM,etal.Moductivationbyantidepressants[J]31-150.DOI:10.1177/026988112ation:asystematicreviewoftheeffectsofstressonmicrogliaandtheimplicationsformentalillness[J].Psychopharmacology(016,233(9):1637-1650.DOI:10.1007/s00213-016-4[10]ColonnaM,Butovsky0.Microgliafunctionin35:441-468.DOI:10.1146/annurev-immunol-05111[11]SaijoK,CrottiA,GlassCK.Regulationofddeactivationbynuclearreceptors[J].Glia,2013,61(1):104-12019,41(14):1301-1307.DOI:10.16016/j.1000-5404stress-induceddepression-likeampalmicrogliaM2polarization[J].JArmyMedUniv,2019,41(14):1301-1307.DOI:10.16016/j.1000-5[13]ScheepstraK,MizeeMR,vanScheppiorticalgraymattermicroglia[J].BiolP29.DOI:10.1016/j.biopsych.2023.04.020.中華行為醫(yī)學(xué)與腦科學(xué)雜志，2023,32(5):467-473.DOI:10.3760/cma.371468-20221211-00747.DongY,GanYX,DongYG,etal.ThemechanismBrainSci,2023,32(5):467-473.DOI:10.3760/371468同活化途徑的影響[J].中華精神科雜志，2014,47(6):364-370.DOI:10.3760/cma.j.issn.1006-7884.2014.06.012.SuF,YiTheeffectoffluoxetineandescitalopglia[J].ChinJPsychiatry,2014,47(6):364-370.DOI:10.3760/cma.[16]LuY,XuX,JiangTCUMSmiceandinhibitsTNF-a-indu[J].IntImmunopharmacol,2019,67:119-128.DOI:10.1016/j病機制的影響[J].醫(yī)學(xué)研究生學(xué)報，2015,28(10):1038-1042.DOI:10.16571/ki.1008-8199.2015.10.007.JiangZL,WangF,XieT,etal.EffectofactivatedmicrogliainducedbyLCN2ondepressionpathogenesisinrats[J].JournalofMedicalPostgraduates,2015,28(10):1038-1042.DOI:10.16571/ki.1008-8199.2015.10.007.[18]WuA,ZhangJ.Neuroinflamachestohippocampalneurogenesis[J].JNeuroinflammation,2023,20(1)283.DOI:10.1186/s12974-023-02inflammasome:isthereacausalrelationshi22,16:1018628.DOI:10.3389/fnins.2022.1[20]DuanN,ZhangY,TanS,etal.TherapeIRF3signallingameliorateschronichavioursbymodulatingneuroinflammationandmicrogliaphagocytosisnofstriatalneurons[J].Immunity,2021,54(2):225-234.e6.DOI:10.allenges[J].BrainBehavImmun,2[23]HuangX,WangB,YangJ,etal.HMGB1indepression:anoverviewmicroglialHMBGlinthepathogenesisofdepression[J].BrainBehav[24]FranklinTC,Wohlebve-likebehavior[J].BiolPsychiatry,2/j.biopsych.2017.06.034.[25]GuoD,XuY,LiuZ,etal.IGF2inhibitshippocampalmicrogliaandalleviatesdepression-likebehaviorinLPS-treatedmalemice[J].Brainnresbull.2023.01.001.[26]BassettB,SubramaniyamS,FanlhippocampusviablrainBehavImmun,2021,91:519-530.DOI:10.1016/j.bbi.20reversesthedepression-associatedbehaviourandregunicmildstress/j.neuroscience.2020.05.014.try,2022,27(3):1618-1629.DOI:10.1038/s41380-021-01377-7.ftheembryonicforebrain[J].CellR10.1016/j.celrep.2014.07.042.[30]SunY,CheJ,ZhangJ.Emergingnon-proinflammatoryrgliainhealthyanddiseasedbrains[J].BrainRes140.MeiYX,ChenX,HuZL,etal.Cluster200(CDadulthippocampus[J].ChinJPharm[32]HanY,ZhangL,WangQ,etal.Minocycvationandalleviatesdeprescesubjectedtomate9,107:37-45.DOI:10.1016/j.psyneuen.2019.04減輕LPS誘導(dǎo)的小鼠神經(jīng)炎性反應(yīng)[J].基礎(chǔ)醫(yī)學(xué)與臨床，2019,39(7):943-948.DOI:10.16352/j.issn.1001-6325.2019.07.004.LiLL,XiuJB,ShenY,etal.MinocyclinealleviatesLPS-inducedneuroinflammationbyincinmice[J].BasicClinMed,2019,39(7):943-948.DOI:10.16352/j.isgeffectsofelectroconvulsivestimulation[J].MolPsychiatry,27(2):1120-1135.DOI:10.1038/s41380-021-01338-0.[35]LiZR,LiuDG,Xairmentofhippocamp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