Ozone inhalation activates stress‐responsive regions of the CNS

Abstract

Ozone (O 3 ), a major component of air pollution, has considerable impact on public health. Besides the well-described respiratory tract inflammation and dysfunctions, there is accumulating evidence indicating that O 3 exposure affects brain functions. However, the mechanisms through which O 3 exerts toxic effects on the brain remain poorly understood. This work aimed at precisely characterizing CNS neuronal activation after O 3 inhalation using Fos staining in adult rat. We showed that, together with lung inflammation, O 3 exposure caused a sustained time-and dose-dependent neuronal activation in the dorsolateral regions of the nucleus tractus solitarius overlapping terminal fields of lung afferents running in vagus nerves. Furthermore, we highlighted neuronal activation in interconnected central structures such as the caudal ventrolateral medulla, the parabrachial nucleus, the central nucleus of the amygdala, the bed nucleus of the stria terminalis and the paraventricular hypothalamic nucleus. In contrast, we did not detect any neuronal activation in the thoracic spinal cord where lung afferents running in spinal nerves terminate. Overall, our results demonstrate that O 3 challenge evokes a lung inflammation that induces the activation of nucleus tractus solitarius neurons through the vagus nerves and promotes neuronal activation in stress-responsive regions of the CNS.

Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans

“…The present human study did not involve ozone exposure during resting and exposure occurred only for 2 hours. Acute ozone exposure has been shown to activate central stress responsive regions and the nucleus tractus solitarius where pulmonary vagal nerves terminate in the brain (18,32). Thus, pulmonary vagal C fibers, likely through neurotransmission in the brain, can stimulate sympathetic and/or the HPA axis, leading to the release of stress hormones from sympathetic nerve endings and also from the adrenal gland (33,34).…”

“…More recently, epidemiologic and experimental studies have associated inhaled pollutants with a variety of neural outcomes (14)(15)(16)(17). Specifically, exposure to ozone activates the nucleus tractus solitarius and stress responsive regions of the hypothalamus through stimulation of pulmonary vagal C fibers (18). Acute ozone exposure can increase levels of circulating stress hormones, such as epinephrine and corticosterone, in rats (19)(20)(21).…”

Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats

“…More specifically, acute O 3 exposure has been shown to stimulate lung vagal C-fibers through transient receptor potential member A1 (TRPA-1) receptors that lead to activation of neural stress-responsive regions in the central nervous system where lung afferents of vagus nerves terminate (Taylor-Clark and Undem, 2010; Gackiere et al, 2011). Stress-mediated hypothalamus pituitary adrenal (HPA) axis activation is well known to modulate a variety of physiological processes including thermoregulation, immune elicitation, hormonal disposition, and systemic metabolic alterations (Ulrich-Lai and Herman, 2009).…”

Air Pollution and Insulin Resistance: Do All Roads Lead to Rome?

“…This is associated with impaired glucose homeostasis (8) and mobilization of energy sources during stress responses, an observation that might coincide with the adaptive insulin resistance in peripheral tissues (9) that was observed in the new work by Vella et al (5). A growing body of evidence supports the hypothesis that ozone exposure induces a neuronal response that activates stress-sensitive centers in the nucleus tractus solitarius (10,11). Activation of catecholaminergic neurons in the nucleus tractus solitariuscentral to systemic sympathetic stimulation-can mediate an immediate action (fight-or-flight response), activate a hypothalamus-pituitary-adrenal-mediated release of hormones from the adrenal cortex (12), and result in a release of glucose, free fatty acids, and branched-chain amino acids into the circulation (Fig.…”