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

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

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Fine particulate matter (PM2.5) is associated with increased risks of Alzheimer'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 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 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 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 and mRNA biomarkers and potential miRNA-mRNA interaction networks of PM2.5-promoted AD.
Original languageEnglish
Pages (from-to)25-40
Number of pages16
JournalJournal of Environmental Sciences
Volume122
Early online dateFeb 2022
DOIs
Publication statusE-pub ahead of print - Feb 2022

Scopus Subject Areas

  • Environmental Science(all)
  • Neuroscience(all)

User-Defined Keywords

  • Fine particulate matter
  • mRNAs
  • miRNAs
  • Brain
  • Alzheimer's disease
  • APP/PS1 transgenic mice

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