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

胎儿期暴露于空气污染颗粒物的小鼠新生儿的大脑皮层和血液转录组变化

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作者:Amin Haghani, Jason I Feinberg, Kristy C Lewis, Christine Ladd-Acosta, Richard G Johnson, Andrew E Jaffe, Constantinos Sioutas, Caleb E Finch, Daniel B Campbell #, Todd E Morgan #, Heather E Volk #

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.

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.

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.

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