Ozone-Induced Dysregulation of Neuroendocrine Axes Requires Adrenal-Derived Stress Hormones

Henriquez, Andres R.; House, John S.; Snow, Samantha J.; Miller, Colette N.; Schladweiler, Mette C.; Fisher, Anna; Ren, Hongzu; Valdez, Matthew; Kodavanti, Prasada R.; Kodavanti, Urmila P.

doi:10.1093/toxsci/kfz182

Ozone-Induced Dysregulation of Neuroendocrine Axes Requires Adrenal-Derived Stress Hormones

Journal Article · Mon Aug 12 00:00:00 EDT 2019 · Toxicological Sciences

DOI:https://doi.org/10.1093/toxsci/kfz182· OSTI ID:2202880

Henriquez, Andres R.; House, John S.; ; Miller, Colette N.; Schladweiler, Mette C.; Fisher, Anna; Ren, Hongzu; Valdez, Matthew; Kodavanti, Prasada R.; Kodavanti, Urmila P.

Abstract

Acute ozone inhalation increases circulating stress hormones through activation of the sympathetic-adrenal-medullary and hypothalamic-pituitary-adrenal axes. Rats with adrenalectomy (AD) have attenuated ozone-induced lung responses. We hypothesized that ozone exposure will induce changes in circulating pituitary-derived hormones and global gene expression in the brainstem and hypothalamus, and that AD will ameliorate these effects. Male Wistar-Kyoto rats (13 weeks) that underwent sham surgery (SHAM) or AD were exposed to ozone (0.8 ppm) or filtered-air for 4 h. In SHAM rats, ozone exposure decreased circulating thyroid-stimulating hormone (TSH), prolactin (PRL), and luteinizing hormone (LH). AD prevented reductions in TSH and PRL, but not LH. AD increased adrenocorticotropic hormone approximately 5-fold in both air- and ozone-exposed rats. AD in air-exposed rats resulted in few significant transcriptional differences in the brainstem and hypothalamus (approximately 20 genes per tissue). In contrast, ozone-exposure in SHAM rats resulted in either increases or decreases in expression of hundreds of genes in the brainstem and hypothalamus relative to air-exposed SHAM rats (303 and 568 genes, respectively). 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-3,4-dihydroxyphenylalanine, 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 upon the presence of circulating adrenal-derived stress hormones. This is likely to have profound downstream influence on systemic effects of ozone.

View Journal Article

Sponsoring Organization:: USDOE

OSTI ID:: 2202880

Journal Information:: Toxicological Sciences, Journal Name: Toxicological Sciences Journal Issue: 1 Vol. 172; ISSN 1096-6080

Publisher:: Oxford University PressCopyright Statement

Country of Publication:: United States

Language:: English

References (57)

Climate Change Patz, Jonathan A.; Frumkin, Howard; Holloway, Tracey JAMA, Vol. 312, Issue 15 https://doi.org/10.1001/jama.2014.13186	journal	October 2014
Modulation of the Inflammatory Effects of Inhaled Ozone in Rats by Subcutaneous Prolactin-Secreting, Pituitary-Derived Tumors Gunnison, A. Fundamental and Applied Toxicology, Vol. 37, Issue 1 https://doi.org/10.1006/faat.1997.2300	journal	May 1997
Hyperthyroidism Increases the Risk of Ozone-Induced Lung Toxicity in Rats Huffman, L. J.; Judy, D. J.; Brumbaugh, K. Toxicology and Applied Pharmacology, Vol. 173, Issue 1 https://doi.org/10.1006/taap.2001.9174	journal	May 2001
The blood-brain barrier for catecholamines — Revisited Kostrzewa, Richard M. Neurotoxicity Research, Vol. 11, Issue 3-4 https://doi.org/10.1007/BF03033571	journal	September 2007
Glucocorticoids and endothelial cell barrier function Salvador, Ellaine; Shityakov, Sergey; Förster, Carola Cell and Tissue Research, Vol. 355, Issue 3 https://doi.org/10.1007/s00441-013-1762-z	journal	December 2013
Regulation of Hypothalamo-Pituitary-Adrenocortical Responses to Stressors by the Nucleus of the Solitary Tract/Dorsal Vagal Complex Herman, James P. Cellular and Molecular Neurobiology, Vol. 38, Issue 1 https://doi.org/10.1007/s10571-017-0543-8	journal	September 2017
Does air pollution trigger suicide? A case-crossover analysis of suicide deaths over the life span Casas, Lidia; Cox, Bianca; Bauwelinck, Mariska European Journal of Epidemiology, Vol. 32, Issue 11 https://doi.org/10.1007/s10654-017-0273-8	journal	June 2017
Air Pollution and Autism Spectrum Disorders: Causal or Confounded? Weisskopf, Marc G.; Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L. Current Environmental Health Reports, Vol. 2, Issue 4 https://doi.org/10.1007/s40572-015-0073-9	journal	September 2015
Developmental Neurotoxicity of Traffic-Related Air Pollution: Focus on Autism Costa, Lucio G.; Chang, Yu-Chi; Cole, Toby B. Current Environmental Health Reports, Vol. 4, Issue 2 https://doi.org/10.1007/s40572-017-0135-2	journal	April 2017
Effect of short-term ozone exposure on exogenous thyroxine levels in thyroidectomized and hypophysectomized rats Clemons, Gisela K.; Wei, Davie Toxicology and Applied Pharmacology, Vol. 74, Issue 1 https://doi.org/10.1016/0041-008X(84)90273-4	journal	June 1984
Mechanisms of the acute effects of inhaled ozone in humans Bromberg, Philip A. Biochimica et Biophysica Acta (BBA) - General Subjects, Vol. 1860, Issue 12 https://doi.org/10.1016/j.bbagen.2016.07.015	journal	December 2016
The Molecular Signatures Database Hallmark Gene Set Collection Liberzon, Arthur; Birger, Chet; Thorvaldsdóttir, Helga Cell Systems, Vol. 1, Issue 6 https://doi.org/10.1016/j.cels.2015.12.004	journal	December 2015
Exposure to air pollution and cognitive functioning across the life course – A systematic literature review Clifford, Angela; Lang, Linda; Chen, Ruoling Environmental Research, Vol. 147 https://doi.org/10.1016/j.envres.2016.01.018	journal	May 2016
Effect of long-term outdoor air pollution and noise on cognitive and psychological functions in adults Tzivian, Lilian; Winkler, Angela; Dlugaj, Martha International Journal of Hygiene and Environmental Health, Vol. 218, Issue 1 https://doi.org/10.1016/j.ijheh.2014.08.002	journal	January 2015
Exposure to air pollution as a potential contributor to cognitive function, cognitive decline, brain imaging, and dementia: A systematic review of epidemiologic research Power, Melinda C.; Adar, Sara D.; Yanosky, Jeff D. NeuroToxicology, Vol. 56 https://doi.org/10.1016/j.neuro.2016.06.004	journal	September 2016
A users guide to HPA axis research Spencer, Robert L.; Deak, Terrence Physiology & Behavior, Vol. 178 https://doi.org/10.1016/j.physbeh.2016.11.014	journal	September 2017
Air pollutants and cough Joad, Jesse P.; Sekizawa, Shin-ichi; Chen, Chao-Yin Pulmonary Pharmacology & Therapeutics, Vol. 20, Issue 4 https://doi.org/10.1016/j.pupt.2006.10.013	journal	August 2007
Self-reported exposure to traffic pollution in relation to daytime sleepiness and habitual snoring: a questionnaire study in seven North-European cities Gislason, Thorarinn; Bertelsen, Randi J.; Real, Francisco Gomez Sleep Medicine, Vol. 24 https://doi.org/10.1016/j.sleep.2016.08.007	journal	August 2016
Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats Bass, V.; Gordon, C. J.; Jarema, K. A. Toxicology and Applied Pharmacology, Vol. 273, Issue 3 https://doi.org/10.1016/j.taap.2013.09.029	journal	December 2013
Inhaled ozone (O3)-induces changes in serum metabolomic and liver transcriptomic profiles in rats Miller, Desinia B.; Karoly, Edward D.; Jones, Jan C. Toxicology and Applied Pharmacology, Vol. 286, Issue 2 https://doi.org/10.1016/j.taap.2015.03.025	journal	July 2015
Systemic metabolic derangement, pulmonary effects, and insulin insufficiency following subchronic ozone exposure in rats Miller, Desinia B.; Snow, Samantha J.; Henriquez, Andres Toxicology and Applied Pharmacology, Vol. 306 https://doi.org/10.1016/j.taap.2016.06.027	journal	September 2016
Adrenal-derived stress hormones modulate ozone-induced lung injury and inflammation Henriquez, Andres; House, John; Miller, Desinia B. Toxicology and Applied Pharmacology, Vol. 329 https://doi.org/10.1016/j.taap.2017.06.009	journal	August 2017
Adrenergic and glucocorticoid receptor antagonists reduce ozone-induced lung injury and inflammation Henriquez, Andres R.; Snow, Samantha J.; Schladweiler, Mette C. Toxicology and Applied Pharmacology, Vol. 339 https://doi.org/10.1016/j.taap.2017.12.006	journal	January 2018
The molecular physiology of CRH neurons Aguilera, Greti; Liu, Ying Frontiers in Neuroendocrinology, Vol. 33, Issue 1 https://doi.org/10.1016/j.yfrne.2011.08.002	journal	January 2012
Air pollution and your brain: what do you need to know right now Calderón-Garcidueñas, Lilian; Calderón-Garcidueñas, Ana; Torres-Jardón, Ricardo Primary Health Care Research & Development, Vol. 16, Issue 04 https://doi.org/10.1017/S146342361400036X	journal	September 2014
Neuronal regulation of type 2 innate lymphoid cells via neuromedin U Cardoso, Vânia; Chesné, Julie; Ribeiro, Hélder Nature, Vol. 549, Issue 7671 https://doi.org/10.1038/nature23469	journal	September 2017
Circumventricular Organs: Definition And Role In The Regulation Of Endocrine And Autonomic Function Ganong, William F. Clinical and Experimental Pharmacology and Physiology, Vol. 27, Issue 5-6 https://doi.org/10.1046/j.1440-1681.2000.03259.x	journal	May 2000
Increased Susceptibility of Hyperthyroid Rats to Ozone: Early Events and Mechanisms Huffman, L. J.; Beighley, C. M.; Frazer, D. G. Journal of Toxicology and Environmental Health, Part A, Vol. 69, Issue 6 https://doi.org/10.1080/15287390500247017	journal	April 2006
Acute Air Pollution Exposure and Risk of Suicide Completion Bakian, A. V.; Huber, R. S.; Coon, H. American Journal of Epidemiology, Vol. 181, Issue 5 https://doi.org/10.1093/aje/kwu341	journal	February 2015
Mapping Acute Systemic Effects of Inhaled Particulate Matter and Ozone: Multiorgan Gene Expression and Glucocorticoid Activity Thomson, Errol M.; Vladisavljevic, Djordje; Mohottalage, Susantha Toxicological Sciences, Vol. 135, Issue 1 https://doi.org/10.1093/toxsci/kft137	journal	June 2013
Acute Ozone-Induced Pulmonary and Systemic Metabolic Effects Are Diminished in Adrenalectomized Rats Miller, Desinia B.; Snow, Samantha J.; Schladweiler, Mette C. Toxicological Sciences, Vol. 150, Issue 2 https://doi.org/10.1093/toxsci/kfv331	journal	January 2016
Aging Exacerbates Neuroinflammatory Outcomes Induced by Acute Ozone Exposure Tyler, Christina R.; Noor, Shahani; Young, Tamara L. Toxicological Sciences, Vol. 163, Issue 1 https://doi.org/10.1093/toxsci/kfy014	journal	January 2018
Neuroendocrine Regulation of Air Pollution Health Effects: Emerging Insights Snow, Samantha J.; Henriquez, Andres R.; Costa, Daniel L. Toxicological Sciences, Vol. 164, Issue 1 https://doi.org/10.1093/toxsci/kfy129	journal	May 2018
Beta-2 Adrenergic and Glucocorticoid Receptor Agonists Modulate Ozone-Induced Pulmonary Protein Leakage and Inflammation in Healthy and Adrenalectomized Rats Henriquez, Andres R.; Snow, Samantha J.; Schladweiler, Mette C. Toxicological Sciences, Vol. 166, Issue 2 https://doi.org/10.1093/toxsci/kfy198	journal	August 2018
Ambient Particulate Matter and Acrolein Co-Exposure Increases Myocardial Dyssynchrony in Mice via TRPA1 Thompson, Leslie C.; Walsh, Leon; Martin, Brandi L. Toxicological Sciences, Vol. 167, Issue 2 https://doi.org/10.1093/toxsci/kfy262	journal	October 2018
ACTH controls thymocyte homeostasis independent of glucocorticoids Talaber, Gergely; Tuckermann, Jan Peter; Okret, Sam The FASEB Journal, Vol. 29, Issue 6 https://doi.org/10.1096/fj.14-268508	journal	March 2015
Microglial priming through the lung–brain axis: the role of air pollution–induced circulating factors Mumaw, Christen L.; Levesque, Shannon; McGraw, Constance The FASEB Journal, Vol. 30, Issue 5 https://doi.org/10.1096/fj.201500047	journal	May 2016
Serum amyloid A: an ozone‐induced circulating factor with potentially important functions in the lung‐brain axis Erickson, Michelle A.; Jude, Joseph; Zhao, Hengjiang The FASEB Journal, Vol. 31, Issue 9 https://doi.org/10.1096/fj.201600857RRR	journal	September 2017
Transient receptor potential channels and occupational exposure Geppetti, Pierangelo; Patacchini, Riccardo; Nassini, Romina Current Opinion in Allergy & Clinical Immunology, Vol. 14, Issue 2 https://doi.org/10.1097/ACI.0000000000000040	journal	April 2014
Ozone inhalation activates stress-responsive regions of the CNS: Fos CNS mapping following ozone inhalation Gackière, Florian; Saliba, Layal; Baude, Agnès Journal of Neurochemistry, Vol. 117, Issue 6 https://doi.org/10.1111/j.1471-4159.2011.07267.x	journal	May 2011
Remodeling of glial coverage of glutamatergic synapses in the rat nucleus tractus solitarii after ozone inhalation Chounlamountry, Keodavanh; Boyer, Bénédicte; Penalba, Virginie Journal of Neurochemistry, Vol. 134, Issue 5 https://doi.org/10.1111/jnc.13193	journal	July 2015
Vagal Afferent Innervation of the Airways in Health and Disease Mazzone, Stuart B.; Undem, Bradley J. Physiological Reviews, Vol. 96, Issue 3 https://doi.org/10.1152/physrev.00039.2015	journal	July 2016
Ozone Exposure Increases Circulating Stress Hormones and Lipid Metabolites in Humans Miller, Desinia B.; Ghio, Andrew J.; Karoly, Edward D. American Journal of Respiratory and Critical Care Medicine, Vol. 193, Issue 12 https://doi.org/10.1164/rccm.201508-1599OC	journal	June 2016
Innate Lymphoid Cells Mediate Pulmonary Eosinophilic Inflammation, Airway Mucous Cell Metaplasia, and Type 2 Immunity in Mice Exposed to Ozone Kumagai, Kazuyoshi; Lewandowski, Ryan P.; Jackson-Humbles, Daven N. Toxicologic Pathology, Vol. 45, Issue 6 https://doi.org/10.1177/0192623317728135	journal	August 2017
Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Love, Michael I.; Huber, Wolfgang; Anders, Simon Genome Biology, Vol. 15, Issue 12 https://doi.org/10.1186/s13059-014-0550-8	journal	December 2014
Air Pollution and Neuropsychological Development: A Review of the Latest Evidence Suades-González, Elisabet; Gascon, Mireia; Guxens, Mònica Endocrinology, Vol. 156, Issue 10 https://doi.org/10.1210/en.2015-1403	journal	August 2015
Corticosteroid Feedback Control of ACTH Secretion: Rapid Effects of Bilateral Adrenalectomy on Plasma ACTH in the Rat1 Dallman, M. F.; Jones, M. T.; Vernikos-Danellis, J. Endocrinology, Vol. 91, Issue 4 https://doi.org/10.1210/endo-91-4-961	journal	October 1972
Association of Ambient Air Pollution with Depressive and Anxiety Symptoms in Older Adults: Results from the NSHAP Study Pun, Vivian C.; Manjourides, Justin; Suh, Helen Environmental Health Perspectives, Vol. 125, Issue 3 https://doi.org/10.1289/EHP494	journal	March 2017
Identification of Candidate Genes Downstream of TLR4 Signaling after Ozone Exposure in Mice: A Role for Heat-Shock Protein 70 Bauer, Alison K.; Rondini, Elizabeth A.; Hummel, Kristin A. Environmental Health Perspectives, Vol. 119, Issue 8 https://doi.org/10.1289/ehp.1003326	journal	August 2011
Traffic-Related Air Pollution, Noise at School, and Behavioral Problems in Barcelona Schoolchildren: A Cross-Sectional Study Forns, Joan; Dadvand, Payam; Foraster, Maria Environmental Health Perspectives, Vol. 124, Issue 4 https://doi.org/10.1289/ehp.1409449	journal	April 2016
The effects of ozone exposure and associated injury mechanisms on the central nervous system Martínez-Lazcano, Juan Carlos; González-Guevara, Edith; del Carmen Rubio, María Reviews in the Neurosciences, Vol. 24, Issue 3 https://doi.org/10.1515/revneuro-2012-0084	journal	January 2013
How air pollution alters brain development: the role of neuroinflammation Brockmeyer, Sam; D’Angiulli, Amedeo Translational Neuroscience, Vol. 7, Issue 1 https://doi.org/10.1515/tnsci-2016-0005	journal	January 2016
Air Pollution and Insulin Resistance: Do All Roads Lead to Rome? Kodavanti, Urmila P. Diabetes, Vol. 64, Issue 3 https://doi.org/10.2337/db14-1682	journal	February 2015
Exposure to ozone induces a systemic inflammatory response: possible source of the neurological alterations induced by this gas González-Guevara, Edith; Martínez-Lazcano, Juan Carlos; Custodio, Verónica Inhalation Toxicology, Vol. 26, Issue 8 https://doi.org/10.3109/08958378.2014.922648	journal	July 2014
Whole body plethysmography reveals differential ventilatory responses to ozone in rat models of cardiovascular disease Dye, Janice A.; Ledbetter, Allen D.; Schladweiler, Mette C. Inhalation Toxicology, Vol. 27, Issue sup1 https://doi.org/10.3109/08958378.2014.954167	journal	March 2015
Severe Urban Outdoor Air Pollution and Children’s Structural and Functional Brain Development, From Evidence to Precautionary Strategic Action D’Angiulli, Amedeo Frontiers in Public Health, Vol. 6 https://doi.org/10.3389/fpubh.2018.00095	journal	April 2018
Biomarkers of Dose and Effect of Inhaled Ozone in Resting versus Exercising Human Subjects: Comparison with Resting Rats Hatch, Gary E.; McKee, John; Brown, James Biomarker Insights, Vol. 8 https://doi.org/10.4137/BMI.S11102	journal	January 2013

Similar Records

Changes in thyroid function after short-term ozone exposure in rats

Journal Article · Mon Dec 31 23:00:00 EST 1979 · J. Environ. Pathol. Toxicol.; (United States) · OSTI ID:6199268

Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats

Journal Article · Thu Jun 23 00:00:00 EDT 2022 · Toxicological Sciences · OSTI ID:1982725

Stress Drivers of Glucose Dynamics during Ozone Exposure Measured Using Radiotelemetry in Rats

Journal Article · Tue Dec 20 19:00:00 EST 2022 · Environmental Health Perspectives · OSTI ID:2425808

Ozone-Induced Dysregulation of Neuroendocrine Axes Requires Adrenal-Derived Stress Hormones

Citation Formats

References (57)

Similar Records

Related Subjects