Fine particulate matter(PM2.5)is associated with increased risks ofAAlzheimer's disease(AD),yet the toxicological mechanisms of PM2.5 promoting AD remain unclear.In this study,wild-type and APP/PS1 transgenic mice(AD mice)were exposed to either filtered air(FA)or PM2.5 for eight weeks with a real-world exposure system in Taiyuan,China(mean PM2.5 concen-tration in the cage was 61 pg/m3).We found that PM2.5 exposure could remarkably aggra-vate AD mice's ethological and brain ultrastructural damage,along with the elevation of the pro-inflammatory cytokines(IL-6 and TNF-α),Aβ-42 and AChE levels and the decline of ChAT levels in the brains.Based on high-throughput sequencing results,some differen-tially expressed(DE)mRNAs and DE miRNAs in the brains of AD mice after PM2.5 exposure were screened.Using RT-qPCR,seven DE miRNAs(mmu-miR-193b-5p,122b-5p,466h-3p,10b-5p,1895,384-5p,and 6412)and six genes(Pcdhgb8,Unc13b,Robo3,Prph,Pter,and Tbata)were evidenced the and verified.Two miRNA-target gene pairs(miR-125b-Pcdhgb8 pair and miR-466h-3p-IL-17Rα/TGF-βR2/Aβ-42/AChE pairs)were demonstrated that they were more related to PM2.5-induced brain injury.Results of Gene Ontology(GO)pathways and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways predicted that synaptic and postsy-naptic regulation,axon guidance,Wnt,MAPK,and mTOR pathways might be the possible regulatory mechanisms associated with pathological response.These revealed that PM2.5-elevated pro-inflammatory cytokine levels and PM2.5-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising miRNA and mRNA biomarkers and potential miRNA-mRNA interaction networks of PM2.5-promoted AD.

Pengfei Fu;Yufei Zhao;Chuan Dong;Zongwei Cai;Ruijin Li;Ken Kin Lam Yung

Department of Biology,Hong Kong Baptist University,Hong Kong SAR,China;Golden Meditech Center for NeuroRegeneration Sciences,Hong Kong Baptist University,Hong Kong SAR,China;Institute of Environmental Science,Shanxi University,Taiyuan 237016,China;State Key Laboratory of Environmental and Biological Analysis,Hong Kong Baptist University,Hong Kong SAR,China

环境科学学报（英文版）

[1]Pengfei Fu;Yufei Zhao;Chuan Dong;Zongwei Cai;Ruijin Li;Ken Kin Lam Yung-.An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM2.5 exposure)[J].环境科学学报（英文版）,2022(12):25-40

ofAAlzheimer,aggra,ethological,466h,Pcdhgb8,Unc13b,Robo3,Prph,Pter,Tbata,postsy,naptic

An,integrative,analysis,expression,brains,disease,transgenic,mice,after,real,world,PM2,exposure,Fine,particulate,matter,associated,increased,risks,AD,yet,toxicological,mechanisms,promoting,remain,unclear,In,this,study,wild,type,PS1,were,exposed,either,filtered,FA,eight,weeks,system,Taiyuan,China,mean,concen,tration,cage,was,pg,We,found,that,could,remarkably,ultrastructural,damage,along,elevation,inflammatory,cytokines,AChE,levels,decline,ChAT,Based,high,throughput,sequencing,results,some,differen,tially,expressed,DE,mRNAs,miRNAs,screened,Using,qPCR,seven,mmu,193b,5p,122b,3p,10b,six,genes,evidenced,verified,Two,target,pairs,125b,17R,TGF,demonstrated,they,more,related,induced,injury,Results,Ontology,pathways,Kyoto,Encyclopedia,Genes,Genomes,predicted,synaptic,regulation,axon,guidance,Wnt,MAPK,mTOR,might,be,possible,regulatory,pathological,response,These,revealed,elevated,altered,neurotransmitter,important,causes,proposed,promising,biomarkers,potential,interaction,networks,promoted

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