Exposure to environmental airborne particulate matter caused wide-ranged transcriptional changes and accelerated Alzheimer's-related pathology: A mouse study

Liron L. Israel, Oliver Braubach, Ekaterina S. Shatalova, Oksana Chepurna, Sachin Sharma, Dmytro Klymyshyn, Anna Galstyan, Antonella Chiechi, Alysia Cox, David Herman, Bishop Bliss, Irene Hasen, Amanda Ting, Rebecca Arechavala, Michael T. Kleinman, Rameshwar Patil, Eggehard Holler, Julia Y. Ljubimova, Maya Koronyo-Hamaoui, Tao SunKeith L. Black

Research output: Contribution to journalArticlepeer-review

2 Scopus citations

Abstract

Air pollution poses a significant threat to human health, though a clear understanding of its mechanism remains elusive. In this study, we sought to better understand the effects of various sized particulate matter from polluted air on Alzheimer's disease (AD) development using an AD mouse model. We exposed transgenic Alzheimer's mice in their prodromic stage to different sized particulate matter (PM), with filtered clean air as control. After 3 or 6 months of exposure, mouse brains were harvested and analyzed. RNA-seq analysis showed that various PM have differential effects on the brain transcriptome, and these effects seemed to correlate with PM size. Many genes and pathways were affected after PM exposure. Among them, we found a strong activation in mRNA Nonsense Mediated Decay pathway, an inhibition in pathways related to transcription, neurogenesis and survival signaling as well as angiogenesis, and a dramatic downregulation of collagens. Although we did not detect any extracellular Aβ plaques, immunostaining revealed that both intracellular Aβ1–42 and phospho-Tau levels were increased in various PM exposure conditions compared to the clean air control. NanoString GeoMx analysis demonstrated a remarkable activation of immune responses in the PM exposed mouse brain. Surprisingly, our data also indicated a strong activation of various tumor suppressors including RB1, CDKN1A/p21 and CDKN2A/p16. Collectively, our data demonstrated that exposure to airborne PM caused a profound transcriptional dysregulation and accelerated Alzheimer's-related pathology.

Original languageEnglish
Article number106307
JournalNeurobiology of Disease
Volume187
DOIs
StatePublished - 15 Oct 2023
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2023 The Authors

Funding

This work was supported by the Health Effects of Air Pollution Foundation (Grant No. BTAP011 , BTAP013 and HEAPF015 ).

FundersFunder number
Health Effects of Air Pollution FoundationBTAP011, BTAP013, HEAPF015

    Keywords

    • Air pollution
    • Alzheimer's disease
    • Neuroinflammation
    • Particulate matter
    • Tumor suppressor
    • β-Amyloid

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