Air Pollutant Impacts on the Brain and Neuroendocrine System with Implications for Peripheral Organs: A Perspective

Air pollutants are increasingly linked to extrapulmonary multi-organ effects. Specifically, recent studies associate air pollutants with brain disorders including psychiatric conditions, neuroinflammation and chronic diseases. Current evidence of linkage between neuropsychiatric conditions and chronic peripheral immune and metabolic diseases, provides insights on the potential role of the neuroendocrine system in mediating neural and systemic effects of inhaled pollutants (reactive particulates and gases). Autonomically-driven stress response, involving sympathetic-adrenal-medullary (SAM) and hypothalamus-pituitary-adrenal (HPA) axes regulate cellular physiological processes through adrenal-derived hormones and diversified receptor systems. Recent experimental evidence demonstrates the contribution of the very stress system responding to non-chemical stressors, in mediating systemic and neural effects of reactive air pollutants. The assessment of how respiratory encounter of air pollutants induce lung and peripheral responses through brain and neuroendocrine system, and how the impairment of these stress pathways could be linked to chronic diseases might help us understand the causes of individual variations in susceptibility and the contribution of habituation/learning and resiliency. This review emphasizes effects of air pollution in the respiratory tract that impact the brain and neuroendocrine system, including the discussion of the role of the potential contribution of autonomic sensory nervous system in triggering neural stress response, the likely contribution of translocated nano particles or metal components, and biological mediators released systemically in causing effects remote to the respiratory tract. The perspective on the use of systems approaches that encompass multiple chemical and non-chemical stressors, including climate-related temperature extremes, with assessment of interactive neural mechanisms and peripheral networks, are emphasized.

Impact/Purpose

In the field of inhalation toxicology and toxicology in general, reversible acute effects induced by environmental stressors have often been considered non-specific. Because these effects are reversible, their inclusion in regulatory decisions have been debated. However, recent studies highlight the significance of these effects linked to injury and inflammation response in the respiratory tract and effects in the brain as well as periphery through neural sympathetic and endocrine systems. The evidence shows that in addition to brain effects of air pollutants, adrenal-derived and other hormones exert their cellular effects through highly diversified adrenergic and glucocorticoid receptors and are involved in respiratory injury and inflammation response. We have shown that in the absence of circulating catecholamines and corticosteroids, ozone-induced lung injury inflammation, peripheral and even brain effects are minimized. The contribution of catecholamines and glucocorticoids continues to be studied in great details since these hormones are implicated in regulating stress response and the plasticity of cellular effects. The essential role of these systems in in mediating air pollution health effect is underappreciated. For example, rarely considered are pharmaceutical agonists and antagonists of these hormones that are extensively used as major therapeutics and their impacts on a range of stressors, including air pollution. Thus, to appropriately examine health outcomes of air pollutants and other stressors, and understand scientific basis for susceptibility variations as well as resiliency, a comprehensive systems approach is needed that encompasses mechanistic assessment of the effects on brain considering temporal aspect, and neuroendocrine pathways, along with stress hormone receptors functionality.    

Citation

Kodavanti, U., T. Jackson, A. Henriquez, S. Snow, D. Alewel, AND D. Costa. Air Pollutant Impacts on the Brain and Neuroendocrine System with Implications for Peripheral Organs: A Perspective. Taylor & Francis, Inc., Philadelphia, PA, 35(3-4):109-126, (2023). [DOI: 10.1080/08958378.2023.2172486]

DOI: Air Pollutant Impacts on the Brain and Neuroendocrine System with Implications for Peripheral Organs: A Perspective