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Ozone exposure differentially changed global gene expression at brainstem and hypothalamus in healthy (SHAM) and adrenalectomized rats

ABSTRACT: Ozone exposure differentially changed global gene expression at brainstem and hypothalamus in healthy (SHAM) and adrenalectomized rats

PROVIDER: PRJNA551004 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR9600960.fastq.gz	Fastqsanger.gz
	SRR9600970.fastq.gz	Fastqsanger.gz
	SRR9600980.fastq.gz	Fastqsanger.gz
	SRR9600961.fastq.gz	Fastqsanger.gz
	SRR9600971.fastq.gz	Fastqsanger.gz

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Ozone exposure differentially changed global gene expression at brainstem and hypothalamus in healthy (SHAM) and adrenalectomized rats

Project description:Ozone exposure in SHAM rats resulted in increases and decreases in expression of hundreds of genes in brainstem and hypothalamus relative to air-exposed SHAM rats (303 and 568 genes, respectively). Adrenalectomy in air-exposed rats resulted in few significant transcriptional differences in the brainstem and hypothalamus (~20 genes per tissue). Differentially expressed genes from ozone exposure were enriched for pathways involving hedgehog signaling, responses to alpha-interferon, hypoxia, and mTORC1, among others. Gene changes in both brain areas were analogous to those altered by corticosteroids and L-dopa, suggesting a role for endogenous glucocorticoids and catecholamines. AD completely prevented this ozone-induced transcriptional response. These findings show that short-term ozone inhalation promotes a shift in brainstem and hypothalamic gene expression that is dependent on the presence of circulating adrenal-derived stress hormones.

2019-12-31 | GSE133293 | GEO

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Project description:Ozone-induced lung injury/inflammation and pulmonary/hypothalamus gene expression are diminished in adrenalectomized (ADREX) rats. Acute ozone exposure induces metabolic alterations concomitant with increases in epinephrine and corticosterone. We hypothesized that adrenal hormones are responsible for observed hepatic ozone effects, and in ADREX rats, these changes would be diminished. Five-seven days after sham or ADREX surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4-hrs. Serum samples were analyzed for metabolites and liver for transcriptional changes immediately post-exposure. Ozone increased circulating triglycerides, cholesterol, free fatty acids, and leptin in sham but not ADREX rats. Ozone-induced inhibition of glucose-mediated insulin release was reversed in ADREX rats. Unlike diminution of hypothalamus and lung mRNA expression changes, ADREX in air-exposed rats (ADREX-air/sham-air) caused differential expression of ~1000 genes in liver. Likewise, ~1000 genes were differentially expressed in ozone-exposed ADREX rats (ADREX-ozone/ADREX-air). Ozone-induced hepatic changes in sham rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified significant similarity to glucocorticoids and pathways involving CREBBP. These changes were absent in ADREX rats exposed to ozone. However, ozone caused unique changes in ADREX liver mRNA reflecting activation of synaptogenesis, neurovascular coupling, neuroinflammation, and insulin signaling with inhibition of senescence pathways. In these rats, upstream predictor analysis identified numerous microRNAs involved under glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and the need for further research elucidating their role in propagating environmentally driven diseases.

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Project description:IUGR is associated with an increased risk of obesity in offspring, which is likely driven in part by reprogramming of the hypothalamus due to suboptimal nutrition and hypoxia during development. As such, we performed mRNA-seq on whole hypothalamic tissue to identify altered expression of genes in our model of IUGR and to identify major pathways that could be associated with fetal undernutrition near term.

2020-11-02 | GSE156859 | GEO

Next Generation Sequencing of lung homogenate mRNA from 8-12 week male C57BL/6 mice following Sham, Carbon Black, Ozone, or Carbon Black-Ozone Co-exposure.

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