An integrative analysis of miRNA and mRNA expression in the brains of Alzheimer's disease transgenic mice after real-world PM2.5 exposure

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


Received July 05, 2021,Revised , Accepted October 06, 2021, Available online February 01, 2022

Volume 34,2022,Pages 25-40

Fine particulatematter (PM2.5) is associated with increased risks of Alzheimer’s disease (AD),yet the toxicologicalmechanisms of PM2.5 promoting AD remain unclear. In this study,wildtype 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 concentration in the cage was 61 μg/m3). We found that PM2.5 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 AChE levels and the decline of ChAT levels in the brains. Based on high-throughput sequencing results, some differentially expressed (DE) mRNAs and DE miRNAs in the brains of AD mice after PM2.5 exposure were screened.Using RT-qPCR, seven DEmiRNAs (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 postsynaptic 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 andmRNA biomarkers and potentialmiRNA-mRNA interaction networks of PM2.5-promoted AD.

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