title: 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.
authors.affiliation: CRN2M, UMR 6231, Centre National de la Recherche Scientifique, Université Paul Cézanne, Université de la Méditerranée, Marseille, France. florian.gackiere@univmed.fr
authors.forename: Florian
authors.initials: F
authors.lastname: Gackière
authors.forename: Layal
authors.initials: L
authors.lastname: Saliba
authors.forename: Agnès
authors.initials: A
authors.lastname: Baude
authors.forename: Olivier
authors.initials: O
authors.lastname: Bosler
authors.forename: Caroline
authors.initials: C
authors.lastname: Strube
mesh_terms: D000280:Administration, Inhalation; D000344:Afferent Pathways / Q000187:drug effects / Q000276:immunology; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001933:Brain Stem / Q000187:drug effects / Q000378:metabolism; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology; D002395:Catecholamines / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000473:pathology; D007962:Leukocytes / Q000187:drug effects / Q000473:pathology; D008168:Lung / Q000187:drug effects / Q000276:immunology / Q000294:innervation; D008297:Male; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D010126:Ozone / Q000008:administration & dosage / Q000633:toxicity*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis; D051381:Rats; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D013312:Stress, Physiological; D014630:Vagus Nerve / Q000187:drug effects / Q000378:metabolism
chemical_list: D002395:Catecholamines; D016760:Proto-Oncogene Proteins c-fos; D010126:Ozone