Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and <i>APOE</i> in <i>Nrf2-Nfkb</i> interactions.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 32579111.
- Also identified by DOI 10.7554/eLife.54822 and PMC identifier 7314548.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The neurotoxicity of air pollution is undefined for sex and <i>APOE</i> alleles. These major risk factors of Alzheimer's disease (AD) were examined in mice given chronic exposure to nPM, a nano-sized subfraction of urban air pollution. In the cerebral cortex, female mice had two-fold more genes responding to nPM than males. Transcriptomic responses to nPM had sex-<i>APOE</i> interactions in AD-relevant pathways. Only <i>APOE</i>3 mice responded to nPM in genes related to Abeta deposition and clearance (<i>Vav2</i>, <i>Vav3</i>, <i>S1009a</i>). Other responding genes included axonal guidance, inflammation (AMPK, NFKB, APK/JNK signaling), and antioxidant signaling (NRF2, HIF1A). Genes downstream of NFKB and NRF2 responded in opposite directions to nPM. <i>Nrf2</i> knockdown in microglia augmented NFKB responses to nPM, suggesting a critical role of NRF2 in air pollution neurotoxicity. These findings give a rationale for epidemiologic studies of air pollution to consider sex interactions with <i>APOE</i> alleles and other AD-risk genes.
Medical subject headings
- Apolipoproteins E
- Brain
- NF-E2-Related Factor 2
- NF-kappa B
- Nanoparticles