Cerebral cortex and blood transcriptome changes in mouse neonates prenatally exposed to air pollution particulate matter

Abstract

Background Prenatal exposure to air pollutants is associated with increased risk for neurodevelopmental and neurodegenerative disorders. However, few studies have identified transcriptional changes related to air pollutant exposure. Methods RNA sequencing was used to examine transcriptomic changes in blood and cerebral cortex of three male and three female mouse neonates prenatally exposed to traffic-related nano-sized particulate matter (nPM) compared to three male and three female mouse neonates prenatally exposed to control filter air. Results We identified 19 nPM-associated differentially expressed genes (nPM-DEGs) in blood and 124 nPM-DEGs in cerebral cortex. The cerebral cortex transcriptional responses to nPM suggested neuroinflammation involvement, including CREB1, BDNF, and IFNγ genes. Both blood and brain tissues showed nPM transcriptional changes related to DNA damage, oxidative stress, and immune responses. Three blood nPM-DEGs showed a canonical correlation of 0.98 with 14 nPM-DEGS in the cerebral cortex, suggesting a convergence of gene expression changes in blood and cerebral cortex. Exploratory sex-stratified analyses suggested a higher number of nPM-DEGs in female cerebral cortex than male cerebral cortex. The sex-stratified analyses identified 2 nPM-DEGs (Rgl2 and Gm37534) shared between blood and cerebral cortex in a sex-dependent manner. Conclusions Our findings suggest that prenatal nPM exposure induces transcriptional changes in the cerebral cortex, some of which are also observed in blood. Further research is needed to replicate nPM-induced transcriptional changes with additional biologically relevant time points for brain development.

Air pollution, dementia, and lifespan in the socio-economic gradient of aging: perspective on human aging for planning future experimental studies

“…Exposure to nPM caused activated glial, and induced inflammation in cerebral cortex, nPM caused 50% increase of microglial CD14 and CD68 and astrocytic GFAP, with 50% higher inflammatory cytokines IL-1α and TNFα. Transcriptional responses include induction of genes for detoxification and oxidative repair via transcription factors Nrf2 and NfkB ( Morgan et al, 2011 ; Zhang et al, 2012 ; Chepelev et al, 2013 ; Haghani et al, 2020b ; Haghani et al, 2021 ). These AirPoll pathways are also shared with systemic oxidative aging processes recognized as a ‘Hallmark of Aging’ ( Schmidlin et al, 2019 ; Maldonaldo et al, 2023 ).…”