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Item High affinity of β-amyloid proteins to cerebral capillaries: implications in chronic lead exposure-induced neurotoxicity in rats(BMC, 2023-05-01) Liu, Luke L.; Shen, Xiaoli; Gu, Huiying; Zhao, Gang; Du, Yansheng; Zheng, Wei; Neurology, School of MedicineLead (Pb) is a known environmental risk factor in the etiology of Alzheimer's disease (AD). The existing reports suggest that Pb exposure increases beta-amyloid (Aβ) levels in brain tissues and cerebrospinal fluid (CSF) and facilitates the formation of amyloid plaques, which is a pathological hallmark for AD. Pb exposure has long been associated with cerebral vasculature injury. Yet it remained unclear if Pb exposure caused excessive Ab buildup in cerebral vasculature, which may damage the blood-brain barrier and cause abnormal Ab accumulation. This study was designed to investigate the impact of chronic Pb exposure on Aβ accumulation in cerebral capillary and the expression of low-density lipoprotein receptor protein-1 (LRP1), a critical Aβ transporter, in brain capillary and parenchyma. Sprague-Dawley rats received daily oral gavage at doses of 0, 14 (low-dose), and 27 (high-dose) mg Pb/kg as Pb acetate, 5 d/wk, for 4 or 8 wks. At the end of Pb exposure, a solution containing Aβ40 was infused into the brain via the cannulated internal carotid artery. Data by ELISA showed a strikingly high affinity of Ab to cerebral vasculature, which was approximately 7-14 times higher than that to the parenchymal fractions collected from control brains. Pb exposure further aggravated the Aβ accumulation in cerebral vasculature in a dose-dependent manner. Western blot analyses revealed that Pb exposure decreased LRP1 expression in cortical capillaries and hippocampal parenchyma. Immunohistochemistry (IHC) studies further revealed a disrupted distribution of LRP1 alongside hippocampal vasculature accompanied with a decreased expression in hippocampal neurons by Pb exposure. Taken together, the current study demonstrated that the cerebral vasculature naturally possessed a high affinity to Aβ present in circulating blood. Pb exposure significantly increased Aβ accumulation in cerebral vasculature; such an increased Aβ accumulation was due partly to the diminished expression of LRP1 in response to Pb in tested brain regions. Perceivably, Pb-facilitated Ab aggravation in cerebral vasculature may contribute to Pb-associated amyloid alterations.Item Positive outcomes from U.S. lead regulations, continued challenges, and lessons learned for regulating emerging contaminants(Springer, 2023) Dietrich, Matthew; Filippelli, Gabriel M.; Earth and Environmental Sciences, School of ScienceAlbeit slow and not without its challenges, lead (Pb) emissions and sources in the United States (U.S.) have decreased immensely over the past several decades. Despite the prevalence of childhood Pb poisoning throughout the twentieth century, most U.S. children born in the last two decades are significantly better off than their predecessors in regard to Pb exposure. However, this is not equal across demographic groups and challenges remain. Modern atmospheric emissions of Pb in the U.S. are nearly negligible since the banning of leaded gasoline in vehicles and regulatory controls on Pb smelting plants and refineries. This is evident in the rapid decrease of atmospheric Pb concentrations across the U.S. over the last four decades. One of the most significant remaining contributors to air Pb is aviation gasoline (avgas), which is minor compared to former Pb emissions. However, continual exposure risks to Pb exist in older homes and urban centers, where leaded paint and/or historically contaminated soils + dusts can still harm children. Thus, while effective in eliminating nearly all primary sources of Pb in the environment, the slow rate of U.S. Pb regulation has led to legacy sources of Pb in the environment. More proactive planning, communication, and research of commonly used emerging contaminants of concern that can persist in the environment long after their initial use (i.e., PFAS) should be prioritized so that the same mistakes are not made again.Item Using community science for detailed pollution research: a case-study approach in Indianapolis, IN, USA(Springer, 2023-01) Dietrich, Matthew; Rader, Shelby T.; Filippelli, Gabriel M.; Earth Science, School of ScienceHeavy metal contamination in urban environments, particularly lead (Pb) pollution, is a health hazard both to humans and ecological systems. Despite wide recognition of urban metal pollution in many cities, there is still relatively limited research regarding heavy metal distribution and transport at the household-scale between soils and indoor dusts-the most important scale for actual human interaction and exposure. Thus, using community-scientist-generated samples in Indianapolis, IN (USA), we applied bulk chemistry, Pb isotopes, and scanning electron microscopy (SEM) to illustrate how detailed analytical techniques can aid in interpretation of Pb pollution distribution at the household-scale. Our techniques provide definitive evidence for Pb paint sourcing in some homes, while others may be polluted with Pb from past industrial/vehicular sources. SEM revealed anthropogenic particles suggestive of Pb paint and the widespread occurrence of Fe-rich metal anthropogenic spherules across all homes, indicative of pollutant transport processes. The variability of Pb pollution at the household scale evident in just four homes is a testament to the heterogeneity and complexity of urban pollution. Future urban pollution research efforts would do well to utilize these more detailed analytical methods on community-sourced samples to gain better insight into where the Pb came from and how it currently exists in the environment. However, these methods should be applied after large-scale pollution screening techniques such as portable X-ray fluorescence (XRF), with more detailed analytical techniques focused on areas where bulk chemistry alone cannot pinpoint dominant pollution mechanisms and where community scientists can also give important metadata to support geochemical interpretations.Item Using community science for detailed pollution research: A case-study approach in Indianapolis, IN, USA(Springer Nature, 2022-11-21) Dietrich, Matthew; Rader, Shelby; Filippelli, Gabriel; Earth and Environmental Sciences, School of ScienceHeavy metal contamination in urban environments, particularly lead (Pb) pollution, is a health hazard both to humans and ecological systems. Despite wide recognition of urban metal pollution in many cities, there is still relatively limited research regarding heavy metal distribution and transport at the household-scale between soils and indoor dusts-the most important scale for actual human interaction and exposure. Thus, using community-scientist-generated samples in Indianapolis, IN (USA), we applied bulk chemistry, Pb isotopes, and scanning electron microscopy (SEM) to illustrate how detailed analytical techniques can aid in interpretation of Pb pollution distribution at the household-scale. Our techniques provide definitive evidence for Pb paint sourcing in some homes, while others may be polluted with Pb from past industrial/vehicular sources. SEM revealed anthropogenic particles suggestive of Pb paint and the widespread occurrence of Fe-rich metal anthropogenic spherules across all homes, indicative of pollutant transport processes. The variability of Pb pollution at the household scale evident in just four homes is a testament to the heterogeneity and complexity of urban pollution. Future urban pollution research efforts would do well to utilize these more detailed analytical methods on community-sourced samples to gain better insight into where the Pb came from and how it currently exists in the environment. However, these methods should be applied after large-scale pollution screening techniques such as portable X-ray fluorescence (XRF), with more detailed analytical techniques focused on areas where bulk chemistry alone cannot pinpoint dominant pollution mechanisms and where community scientists can also give important metadata to support geochemical interpretations.Item Using community science for detailed pollution research: A case-study approach in Indianapolis, IN, USA(Springer, 2023-01) Dietrich, Matthew; Rader, Shelby T.; Filippelli, Gabriel M.; Earth and Environmental Sciences, School of ScienceHeavy metal contamination in urban environments, particularly lead (Pb) pollution, is a health hazard both to humans and ecological systems. Despite wide recognition of urban metal pollution in many cities, there is still relatively limited research regarding heavy metal distribution and transport at the household-scale between soils and indoor dusts—the most important scale for actual human interaction and exposure. Thus, using community-scientist-generated samples in Indianapolis, IN (USA), we applied bulk chemistry, Pb isotopes, and scanning electron microscopy (SEM) to illustrate how detailed analytical techniques can aid in interpretation of Pb pollution distribution at the household-scale. Our techniques provide definitive evidence for Pb paint sourcing in some homes, while others may be polluted with Pb from past industrial/vehicular sources. SEM revealed anthropogenic particles suggestive of Pb paint and the widespread occurrence of Fe-rich metal anthropogenic spherules across all homes, indicative of pollutant transport processes. The variability of Pb pollution at the household scale evident in just four homes is a testament to the heterogeneity and complexity of urban pollution. Future urban pollution research efforts would do well to utilize these more detailed analytical methods on community-sourced samples to gain better insight into where the Pb came from and how it currently exists in the environment. However, these methods should be applied after large-scale pollution screening techniques such as portable X-ray fluorescence (XRF), with more detailed analytical techniques focused on areas where bulk chemistry alone cannot pinpoint dominant pollution mechanisms and where community scientists can also give important metadata to support geochemical interpretations.