Work

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

Year: 2020

Type: article

Abstract: 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.

Source: eLife

DOI: 10.7554/elife.54822

Authors: Amin Haghani, Mafalda Cacciottolo, Kevin R Doty, Carla D'Agostino, Max Thorwald, Nikoo Safi, Morgan E Levine, Constantinos Sioutas, Terrence C Town, Henry Jay Forman, Hongqiao Zhang, Todd E Morgan, Caleb E Finch

Institutions: University of Southern California, Yale University

Language: English

Topic: Air Quality and Health Impacts

Subfield: Health, Toxicology and Mutagenesis

Field: Environmental Science

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $2,500

Funders: Cure Alzheimer's Fund, Viterbi School of Engineering, University of Southern California, National Institute on Aging, National Institute of Neurological Disorders and Stroke

Awards: Amyloid and inflammation: modulation by apoE, gender, air pollution, and drugs, Innate Immune IL-10/STAT3 Signaling in Alzheimer's Disease, Urban Air Pollution and Alzheimer's Disease: Risk, Heterogeneity, and Mechanisms, Identifying the molecular systems, networks, and key molecules that underlie cognitive resilience, G453222670, Peripheral TGF-beta Pathway Inhibitor Therapy in Alzheimer's Rats, Alzheimer Disease Research Center, Molecular mechanisms and social constructs: How genes and environment regulate the rate of aging, Molecular Networks Underlying Resilience to Alzheimer's Disease Among APOE E4 Carriers, Multidisciplinary Research Training in Gerontology, USC-Buck Geroscience Training in the Biology of Aging, Alzheimer's Disease Research Centers, G918963940

OpenAlex ID: W3037513633

FWCI: 2.199

Cites: 78

Cited by: 37

Related to: 10