TY - JOUR TI - Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions AU - Haghani, Amin AU - Cacciottolo, Mafalda AU - Doty, Kevin R AU - D'Agostino, Carla AU - Thorwald, Max AU - Safi, Nikoo AU - Levine, Morgan E AU - Sioutas, Constantinos AU - Town, Terrence C AU - Forman, Henry Jay AU - Zhang, Hongqiao AU - Morgan, Todd E AU - Finch, Caleb E A2 - VijayRaghavan, K A2 - Liu, Riu-Ming VL - 9 PY - 2020 DA - 2020/06/24 SP - e54822 C1 - eLife 2020;9:e54822 DO - 10.7554/eLife.54822 UR - https://doi.org/10.7554/eLife.54822 AB - The neurotoxicity of air pollution is undefined for sex and APOE 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-APOE interactions in AD-relevant pathways. Only APOE3 mice responded to nPM in genes related to Abeta deposition and clearance (Vav2, Vav3, S1009a). 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. Nrf2 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 APOE alleles and other AD-risk genes. KW - air pollution KW - APOE KW - sex KW - Nrf2 KW - nf-kb KW - transcriptome JF - eLife SN - 2050-084X PB - eLife Sciences Publications, Ltd ER -