An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM_(2.5)exposure

查看全文 作　　者：Pengfei [1,2]Fu;Yufei [3]Zhao;Chuan [3]Dong;Zongwei [4]Cai;Ruijin [3]Li;Ken Kin Lam [1,2]Yung

机构地区：[1]Department of Biology,Hong Kong Baptist University,Hong Kong SAR,China;[2]Golden Meditech Center for NeuroRegeneration Sciences,Hong Kong Baptist University,Hong Kong SAR,China;[3]Institute of Environmental Science,Shanxi University,Taiyuan 237016,China;[4]State Key Laboratory of Environmental and Biological Analysis,Hong Kong Baptist University,Hong Kong SAR,China

出　　处：《Journal of Environmental Sciences》索引2022年第34卷第12期,共16页

基　　金：supported by the National Natural Science Foundation of China(No.91843301);the Hundred Talents Program of Shanxi Province in China,and the Hong Kong Research Grants Council Research Matching Scheme(RMGS2019-1-12,RMGS-2019-1-15)。 摘　　要：Fine particulate matter(PM_(2.5))is associated with increased risks of Alzheimer's disease(AD),yet the toxicological mechanisms of PM_(2.5)promoting AD remain unclear.In this study,wildtype and APP/PS1 transgenic mice(AD mice)were exposed to either filtered air(FA)or PM_(2.5)for eight weeks with a real-world exposure system in Taiyuan,China(mean PM_(2.5)concentration in the cage was 61μg/m~3).We found that PM_(2.5)exposure could remarkably aggravate 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 ACh E levels and the decline of Ch AT levels in the brains.Based on high-throughput sequencing results,some differentially expressed(DE)m RNAs and DE mi RNAs in the brains of AD mice after PM_(2.5)exposure were screened.Using RT-q PCR,seven DE mi RNAs(mmu-mi R-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 mi RNA-target gene pairs(mi R-125b-Pcdhgb8 pair and mi R-466h-3p-IL-17Rα/TGF-βR2/Aβ-42/ACh E pairs)were demonstrated that they were more related to PM_(2.5)-induced brain injury.Results of Gene Ontology(GO)pathways and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathways predicted that synaptic and postsynaptic regulation,axon guidance,Wnt,MAPK,and m TOR pathways might be the possible regulatory mechanisms associated with pathological response.These revealed that PM_(2.5)-elevated pro-inflammatory cytokine levels and PM_(2.5)-altered neurotransmitter levels in AD mice could be the important causes of brain damage and proposed the promising mi RNA and m RNA biomarkers and potential mi RNA-m RNA interaction networks of PM_(2.5)-promoted AD. 关键词：Fine particulate matter MRNAS MIRNAS Brain Alzheimer’s disease APP/PS1 transgenic mice

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An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM_(2.5)exposure

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