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.
With wildfires increasing in activity in the Western United States and around the world, there is an immediate need to understand the toxic effects of the smoke. This chapter will provide a background of toxicology and apply principle concepts such as dose, duration and frequency to help define the potential effects of smoke exposure. Characteristics that influence toxicity will be discussed, which include particle size, source and temperature and the mixture of chemical constituents. An overview of the routes of exposure, mechanisms of action, toxicokinetics and the role of the immune system will all be covered.The importance and mutual benefits of in vitro, ex vivo and in vivo studies will be discussed. Finally, the chapter concludes by outlining knowledge gaps and research needs.
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.
Background: Visual disturbances often precede cognitive dysfunction in patients with Alzheimer’s disease (AD) and may coincide with early accumulation of amyloid-β (Aβ) protein in the retina. These findings have inspired critical research on in vivo ophthalmic Aβ 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 cell (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 Aβ 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 Aβ 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.
Due to the high prevalence of opioid prescription following orthopedic procedures, there is a growing need to establish an animal model system to evaluate the effects of opioids on bone remodeling. Rabbits have been employed as model organisms in orthopedic research as they exhibit well-defined cortical bone remodeling similar to humans. Existing research in rabbits has been limited to modes of opioid administration that are short-acting and require repeated application. Here, we present data from a proof-of-principle longitudinal study employing two opioid analgesic administration routes (subcutaneous injection and transdermal patch) to evaluate the efficacy of studying chronic opioid exposure in a rabbit model. Skeletally mature male New Zealand White rabbits (Oryctolagus cuniculus) were divided into three groups of seven animals: morphine, fentanyl, and control. Experimental treatments were conducted for eight weeks. Preparation of the skin at the fentanyl patch site and subsequent patch removal presented experimental difficulties including consistent skin erythema. Though noninvasive, the patches further caused acute stress in fentanyl animals. We conclude that though transdermal fentanyl patches may be preferred in an acute clinical setting, this method is not feasible as a means of long-term pain relief or opioid delivery in a laboratory context.
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