Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions
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...
| Main Authors: | , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
eLife Sciences Publications Ltd
2020-06-01
|
| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/54822 |
| _version_ | 1828107737258524672 |
|---|---|
| author | 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 |
| author_facet | 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 |
| author_sort | Amin Haghani |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-11T10:35:41Z |
| format | Article |
| id | doaj.art-5fa0c904d51e484a90e16f594b2bc0ac |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-04-11T10:35:41Z |
| publishDate | 2020-06-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-5fa0c904d51e484a90e16f594b2bc0ac2022-12-22T04:29:18ZengeLife Sciences Publications LtdeLife2050-084X2020-06-01910.7554/eLife.54822Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactionsAmin Haghani0https://orcid.org/0000-0002-6052-8793Mafalda Cacciottolo1Kevin R Doty2Carla D'Agostino3Max Thorwald4Nikoo Safi5Morgan E Levine6https://orcid.org/0000-0001-9890-9324Constantinos Sioutas7Terrence C Town8Henry Jay Forman9Hongqiao Zhang10Todd E Morgan11Caleb E Finch12https://orcid.org/0000-0002-7617-3958Leonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesZilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesDepartment of Pathology, Yale School of Medicine, New Haven, United StatesDepartment of Civil and Environmental Engineering, Viterbi School of Engineering, University of Southern California, Los Angeles, United StatesZilkha Neurogenetic Institute, Department of Physiology and Neuroscience, Keck School of Medicine of the University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United StatesLeonard Davis School of Gerontology, University of Southern California, Los Angeles, United States; Dornsife College, University of Southern California, Los Angeles, United StatesThe 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.https://elifesciences.org/articles/54822air pollutionAPOEsexNrf2nf-kbtranscriptome |
| spellingShingle | 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 Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions eLife air pollution APOE sex Nrf2 nf-kb transcriptome |
| title | Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions |
| title_full | Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions |
| title_fullStr | Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions |
| title_full_unstemmed | Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions |
| title_short | Mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and APOE in Nrf2-Nfkb interactions |
| title_sort | mouse brain transcriptome responses to inhaled nanoparticulate matter differed by sex and apoe in nrf2 nfkb interactions |
| topic | air pollution APOE sex Nrf2 nf-kb transcriptome |
| url | https://elifesciences.org/articles/54822 |
| work_keys_str_mv | AT aminhaghani mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT mafaldacacciottolo mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT kevinrdoty mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT carladagostino mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT maxthorwald mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT nikoosafi mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT morganelevine mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT constantinossioutas mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT terrencectown mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT henryjayforman mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT hongqiaozhang mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT toddemorgan mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions AT calebefinch mousebraintranscriptomeresponsestoinhalednanoparticulatematterdifferedbysexandapoeinnrf2nfkbinteractions |