Chronic environmental dust exposures are associated with lung inflammation and neuroinflammatory pathology in mice

Organic dusts such as those found in agricultural environments have been previously demonstrated to contain pro-inflammatory compounds and have been linked to chronic pulmonary disease in exposed individuals. More recently these exposures have also been correlated to an increased risk of dementia. Recent findings in our laboratory using a murine model of 3-week repetitive dust exposures identified an increase in pulmonary and neurological inflammation. In these studies, mice co-treated with Resolvin D1 (an omega-3 fatty acid metabolite) exhibited reduced pulmonary inflammation and gliosis, suggesting a protective effect. To further elucidate the impacts of chronic environmental dust exposure on neuroinflammation, and the potential role(s) of omega-3 fatty acids in protecting against dust-induced inflammatory pathology, we performed a chronic (12-week) repetitive exposure study utilizing WT (C57Bl/6) and fat-1 transgenic mice (having increased omega-3 fatty acid tissue composition). Here, WT and fat-1 mice were given intranasal instillations of 12.5% dust extract (DE) 4 times/week for 12 weeks, then sacrificed 72 hours following the final DE challenge. Lungs and brains were fixed in 10% formalin, paraffin embedded and stained with hematoxylin and eosin for histopathological assessment. Examination of lung tissues revealed increases in multiple pathological scoring parameters, including peribronchial inflammation, perivascular inflammation, lymphoid aggregate formation, and epithelial hyperplasia within DE-exposed mice compared to saline-instilled controls. Notably, a survey of the cortex, hippocampus, and olfactory bulb following immunohistochemical staining for Ionized calcium binding adaptor molecule 1 (Iba1) demonstrated a noticeable increase in microglial cells. Studies evaluating differing impacts in WT vs. fat-1 animals are ongoing and may shed light on the role(s) of omega-3 fatty acids in regulating lung and neuro-inflammatory responses to chronic dust exposures. Together, our initial findings implicate chronic dust exposure in promoting early indicators of neuroinflammation—a known hallmark in neurodegenerative disease. These data validate the need for further studies focusing on how environmental exposures increase risk for pulmonary and neurological disorders through systemic inflammatory pathways. R01HL158926 This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.