Indoor Air Quality Considerations for Laboratory Animals in Wildfire-Impacted Regions-A Pilot Study.

Wildfire events are increasing across the globe. The smoke generated as a result of this changing fire landscape is potentially more toxic than air pollution from other ambient sources, according to recent studies. This is especially concerning for populations of humans or animals that live downwind of areas that burn frequently, given that ambient exposure to wildfire smoke cannot be easily eliminated. We hypothesized that a significant indoor air pollution risk existed for laboratory animal facilities located proximal to fire-prone areas. Here, we measured real time continuous outdoor and indoor air quality for 28 days at a laboratory animal facility located in the Rocky Mountain region. We demonstrated that during a wildfire event, the indoor air quality of this animal facility is influenced by ambient smoke events. The daily average indoor fine particulate matter value in an animal room exceeded the Environmental Protection Agency's ambient annual standard 14% of the time and exceeded the World Health Organization's ambient annual guideline 71% of the time. We further show that specialized cage filtration systems are capable of mitigating air pollution penetrance and could improve an animal's microenvironment. The potential effects for laboratory animal physiology that occur in response to the exposure levels and durations measured in this study remain to be determined; yet, even acute wildfire exposure events have been previously correlated with significant differences in gene regulatory and metabolic processes in vivo. We believe these findings warrant consideration for indoor laboratory animal facility air quality monitoring and development of smoke exposure prevention and response protocols, especially among facilities located downwind of fire-prone landscapes.

Alterations in Retinal Signaling Across Age and Sex in 3xTg Alzheimer's Disease Mice.

BACKGROUND: Visual disturbances often precede cognitive dysfunction in patients with Alzheimer's disease (AD) and may coincide with early accumulation of amyloid-ß (Aß) protein in the retina. These findings have inspired critical research on in vivo ophthalmic Aß imaging for disease biomarker detection but have not fully answered mechanistic questions on how retinal pathology affects visual signaling between the eye and brain. OBJECTIVE: The goal of this study was to provide a functional and structural assessment of eye-brain communication between retinal ganglion cells (RGCs) and their primary projection target, the superior colliculus, in female and male 3xTg-AD mice across disease stages. METHODS: Retinal electrophysiology, axonal transport, and immunofluorescence were used to determine RGC projection integrity, and retinal and collicular Aß levels were assessed with advanced protein quantitation techniques. RESULTS: 3xTg mice exhibited nuanced deficits in RGC electrical signaling, axonal transport, and synaptic integrity that exceeded normal age-related decrements in RGC function in age- and sex-matched healthy control mice. These deficits presented in sex-specific patterns among 3xTg mice, differing in the timing and severity of changes. CONCLUSION: These data support the premise that retinal Aß is not just a benign biomarker in the eye, but may contribute to subtle, nuanced visual processing deficits. Such disruptions might enhance the biomarker potential of ocular amyloid and differentiate patients with incipient AD from patients experiencing normal age-related decrements in visual function.

Simulated Wildfire Smoke Significantly Alters Sperm DNA Methylation Patterns in a Murine Model.

Wildfires are now a common feature of the western US, increasing in both intensity and number of acres burned over the last three decades. The effects of this changing wildfire and smoke landscape are a critical public and occupational health issue. While respiratory morbidity due to smoke exposure is a priority, evaluating the molecular underpinnings that explain recent extrapulmonary observations is necessary. Here, we use an Apoe-/- mouse model to investigate the epigenetic impact of paternal exposure to simulated wildfire smoke. We demonstrate that 40 days of exposure to smoke from Douglas fir needles induces sperm DNA methylation changes in adult mice. DNA methylation was measured by reduced representation bisulfite sequencing and varied significantly in 3353 differentially methylated regions, which were subsequently annotated to 2117 genes. The differentially methylated regions were broadly distributed across the mouse genome, but the vast majority (nearly 80%) were hypermethylated. Pathway analyses, using gene-derived and differentially methylated region-derived gene ontology terms, point to a number of developmental processes that may warrant future investigation. Overall, this study of simulated wildfire smoke exposure suggests paternal reproductive risks are possible with prolonged exposure.

Influence of Woodsmoke Exposure on Molecular Mechanisms Underlying Alzheimer's Disease: Existing Literature and Gaps in Our Understanding.

Woodsmoke poses a significant health risk as a growing component of ambient air pollution in the United States. While there is a long history of association between woodsmoke exposure and diseases of the respiratory, circulatory, and cardiovascular systems, recent evidence has linked woodsmoke exposure to cognitive dysfunction, including Alzheimer's disease dementia. Alzheimer's disease is a progressive neurodegenerative disorder with largely idiopathic origins and no known cure. Here, we explore the growing body of literature which relates woodsmoke-generated and ambient air pollution particulate matter exposure to Alzheimer's disease (AD) onset or exacerbation, in the context of an inflammation-centric view of AD. Epigenetic modifications, specifically changes in DNA methylation patterns, are well documented following woodsmoke exposure and have been shown to influence disease-favoring inflammatory cascades, induce oxidative stress, and modulate the immune response in vitro, in vivo, and in humans following exposure to air pollution. Though the current status of the literature does not allow us to draw definitive conclusions linking these events, this review highlights the need for additional work to fill gaps in our understanding of the directionality, causality, and susceptibility throughout the life course.