Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and < i > APOE < /i > in < i > Nrf2-Nfkb < /i > interactions

The neurotoxicity of air pollution is undefined for sex andAPOE 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. OnlyAPOE3 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 withAPOE alleles and other AD-risk genes.
Source: eLife - Category: Biomedical Science Tags: Computational and Systems Biology Neuroscience Source Type: research