Stress hormones as potential mediators of air pollutant effects on the brain: Rapid induction of glucocorticoid-responsive genes
- DOI
- Language of the publication
- English
- Date
- 2019-09-04
- Type
- Article
- Author(s)
- Thomson, Errol M.
- Filiatreault, Alain
- Guénette, Josée
- Publisher
- Elsevier
Abstract
Air pollution is associated with adverse effects on brain health including cognitive decline, dementia, anxiety, depression, and suicide. While toxicological studies have demonstrated the potential for repeated or chronic pollutant exposure to lead to disease states, characterisation of initial biological responses to exposure is needed to better understand underlying mechanisms. The brain is highly sensitive to glucocorticoids (primarily cortisol in humans, corticosterone in rodents), stress hormones that play important roles in cognition and mental health. We tested whether glucocorticoids could be implicated in central nervous system (CNS) effects of pollutant exposure by examining glucocorticoid-dependent signaling across brain regions after exposure to the common pollutant ozone. Male Fischer-344 rats were exposed for 4 h to air or 0.8 ppm ozone ± metyrapone (50 mg/kg), a drug that blocks corticosterone synthesis (n = 5/group). Key glucocorticoid-responsive genes (serum- and glucocorticoid-inducible kinase, SGK; glucocorticoid-inducible leucine zipper, GILZ), and a gene responsive to both glucocorticoids and oxidative stress (metallothionein (MT)-1), were increased by ozone in all brain regions (olfactory bulb, frontal lobe, cortex, midbrain, hippocampus, cerebellum, brainstem), correlating with plasma corticosterone levels. Metyrapone prevented the increase in SGK and GILZ, and reduced but did not eliminate the effect on MT-1, suggesting glucocorticoid-dependent and –independent regulation. Administering exogenous corticosterone (10 mg/kg) to air-exposed rats reproduced the ozone effects, confirming specificity. The results demonstrate that early pollutant effects include stress hormone-dependent signaling. As both ozone and particulate matter activate the hypothalamic-pituitary-adrenal axis, and elevated glucocorticoids are implicated in brain pathologies, stress hormones could contribute to CNS impacts of air pollutants.
Plain language summary
Health Canada is responsible for assessing the health risks associated with exposure to air pollution. Population studies have shown that exposure to air pollution is associated with adverse effects on the brain, including increased incidence of brain-related disorders such as cognitive decline, dementia, depression, and suicide. The brain is exquisitely sensitive to stress hormones, but it is unknown whether stress hormones mediate effects of pollutants on the brain. Health Canada scientists tested whether air pollutants can impact the brain via stress hormones. They found that effects of the pollutant ozone on various brain regions were prevented using a drug that blocked stress hormone production. They also showed that injecting the stress hormone into animals exposed only to air reproduced the effects of ozone. Together, these results confirm that stress hormones can mediate effects of pollutants on the brain. This work provides a potential explanation for how air pollution can adversely impact the brain, substantiating findings in population studies in support of risk assessment initiatives.
Subject
- Health,
- Health and safety