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

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. Overall design: Adult SHAM and adrenalectomized rats were exposed to filtered air or ozone (0.8 ppm, whole-body) for 4hr (~0700 - 1100 AM). Immediately after, hypothalamus and brainstem were collected and frozen.Later, RNA was extracted and sequenced.