Dataset Information

Neuropathology changed by 3- and 6-months low-level PM_2.5 inhalation exposure in spontaneously hypertensive rats.

ABSTRACT:

Background

Epidemiological evidence has linked fine particulate matter (PM_2.5) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM_2.5 on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 months of whole-body exposure to urban PM_2.5 in spontaneously hypertensive (SH) rats.

Results

SH rats were exposed to S-, K-, Si-, and Fe-dominated PM_2.5 at 8.6 ± 2.5 and 10.8 ± 3.8 μg/m³ for 3 and 6 months, respectively. We observed no significant alterations in the escape latency, distance moved, mean area crossing, mean time spent, or mean swimming velocity after PM_2.5 exposure. Notably, levels of MDA had significantly increased in the olfactory bulb, hippocampus, and cortex after 6 months of PM_2.5 exposure (p < 0.05). We observed that 3 months of exposure to PM_2.5 caused significantly higher expressions of t-tau and p-tau in the olfactory bulb (p < 0.05) but not in other brain regions. Beclin 1 was overexpressed in the hippocampus with 3 months of PM_2.5 exposure, but significantly decreased in the cortex with 6 months exposure to PM_2.5. Neuron numbers had decreased with caspase-3 activation in the cerebellum, hippocampus, and cortex after 6 months of PM_2.5 exposure.

Conclusions

Chronic exposure to low-level PM_2.5 could accelerate the development of neurodegenerative pathologies in subjects with hypertension.

SUBMITTER: Chuang HC

PROVIDER: S-EPMC7691081 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Neuropathology changed by 3- and 6-months low-level PM<sub>2.5</sub> inhalation exposure in spontaneously hypertensive rats.

Chuang Hsiao-Chi HC Chen Hsin-Chang HC Chai Pei-Jui PJ Liao Ho-Tang HT Wu Chang-Fu CF Chen Chia-Ling CL Jhan Ming-Kai MK Hsieh Hui-I HI Wu Kuen-Yuh KY Chen Ta-Fu TF Cheng Tsun-Jen TJ

Particle and fibre toxicology 20201126 1

<h4>Background</h4>Epidemiological evidence has linked fine particulate matter (PM<sub>2.5</sub>) to neurodegenerative diseases; however, the toxicological evidence remains unclear. The objective of this study was to investigate the effects of PM<sub>2.5</sub> on neuropathophysiology in a hypertensive animal model. We examined behavioral alterations (Morris water maze), lipid peroxidation (malondialdehyde (MDA)), tau and autophagy expressions, neuron death, and caspase-3 levels after 3 and 6 mon ...[more]

PMID: 33243264

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Project description:BackgroundParticulate matter exposure is associated with respiratory and cardiovascular system dysfunction. Recently, we demonstrated that fine particles, also named PM2.5, modify the expression of some components of the angiotensin and bradykinin systems, which are involved in lung, cardiac and renal regulation. The endocrine kidney function is associated with the regulation of angiotensin and bradykinin, and it can suffer damage even as a consequence of minor alterations of these systems. We hypothesized that exposure to PM2.5 can contribute to early kidney damage as a consequence of an angiotensin/bradykinin system imbalance, oxidative stress and/or inflammation.ResultsAfter acute and subchronic exposure to PM2.5, lung damage was confirmed by increased bronchoalveolar lavage fluid (BALF) differential cell counts and a decrease of surfactant protein-A levels. We observed a statistically significant increment in median blood pressure, urine volume and water consumption after PM2.5 exposure. Moreover, increases in the levels of early kidney damage markers were observed after subchronic PM2.5 exposure: the most sensitive markers, β-2-microglobulin and cystatin-C, increased during the first, second, sixth and eighth weeks of exposure. In addition, a reduction in the levels of specific cytokines (IL-1β, IL-6, TNF-α, IL-4, IL-10, INF-γ, IL-17a, MIP-2 and RANTES), and up-regulated angiotensin and bradykinin system markers and indicators of a depleted antioxidant response, were also observed. All of these effects are in concurrence with the presence of renal histological lesions and an early pro-fibrotic state.ConclusionSubchronic exposure to PM2.5 induced an early kidney damage response that involved the angiotensin/bradykinin systems as well as antioxidant and immune imbalance. Our study demonstrates that PM2.5 can induce a systemic imbalance that not only affects the cardiovascular system, but also affects the kidney, which may also overall contribute to PM-related diseases.

Project description:RationalePrevious studies identified a defect in Ang III (angiotensin III [des-aspartyl1-angiotensin II])-elicited AT2R (Ang type-2 receptor)-mediated natriuresis in renal proximal tubule cells of spontaneously hypertensive rats (SHR).ObjectiveThis study aimed to delineate in prehypertensive SHR kidneys the receptor or postreceptor defect causing impaired AT2R signaling and renal sodium (Na+) retention by utilizing the selective AT2R agonist compound-21 (C-21).Methods and resultsFemale 4-week-old Wistar Kyoto and SHR rats were studied after 24-hour systemic AT1R (Ang II type-1 receptor) blockade. Left kidneys received 30-minute renal interstitial infusions of vehicle followed by C-21 (20, 40, and 60 ng/[kg·min], each dose 30 minutes). Right kidneys received vehicle infusions. In Wistar Kyoto, C-21 dose-dependently increased urine Na+ excretion from 0.023±0.01 to 0.064±0.02, 0.087±0.01, and 0.089±0.01 µmol/min (P=0.008, P<0.0001, and P<0.0001, respectively) and renal interstitial fluid levels of AT2R downstream signaling molecule cGMP (cyclic guanosine 3',5' monophosphate) from 0.91±0.3 to 3.1±1.0, 5.9±1.2 and 5.3±0.5 fmol/mL (P=nonsignificant, P<0.0001, and P<0.0001, respectively). In contrast, C-21 did not increase urine Na+ excretion or renal interstitial cGMP in SHR. Mean arterial pressure was slightly higher in SHR but within the normotensive range and unaffected by C-21. In Wistar Kyoto, but not SHR, C-21 induced AT2R translocation to apical plasma membranes of renal proximal tubule cells, internalization/inactivation of NHE-3 (sodium-hydrogen exchanger-3) and Na+/K+ATPase (sodium-potassium-atpase) and phosphorylation of AT2R-cGMP downstream signaling molecules Src (Src family kinase), ERK (extracellular signal-related kinase), and VASP (vasodilator-stimulated phosphoprotein). To test whether cGMP could bypass the natriuretic defect in SHR, we infused 8-bromo-cGMP. This restored natriuresis, Na+ transporter internalization/inactivation, and Src and VASP phosphorylation, but not apical plasma membrane AT2R recruitment. In contrast, 8-bromo-cAMP administration had no effect on natriuresis or AT2R recruitment in SHR.ConclusionsThe results demonstrate a primary renal proximal tubule cell AT2R natriuretic defect in SHR that may contribute to the development of hypertension. Since the defect is abrogated by exogenous intrarenal cGMP, the renal cGMP pathway may represent a viable target for the treatment of hypertension. Visual Overview: An online visual overview is available for this article.

Project description:IntroductionDespite the London Underground (LU) handling on average 2.8 million passenger journeys per day, the characteristics and potential health effects of the elevated concentrations of metal-rich PM2.5 found in this subway system are not well understood.MethodsSpatial monitoring campaigns were carried out to characterise the health-relevant chemical and physical properties of PM2.5 across the LU network, including diurnal and day-to-day variability and spatial distribution (above ground, depth below ground and subway line). Population-weighted station PM2.5 rankings were produced to understand the relative importance of concentrations at different stations and on different lines.ResultsThe PM2.5 mass in the LU (mean 88 μg m-3, median 28 μg m-3) was greater than at ambient background locations (mean 19 μg m-3, median 14 μg m-3) and roadside environments in central London (mean 22 μg m-3, median 14 μg m-3). Concentrations varied between lines and locations, with the deepest and shallowest submerged lines being the District (median 4 μg m-3) and Victoria (median 361 μg m-3 but up to 885 μg m-3). Broadly in agreement with other subway systems around the world, sampled LU PM2.5 comprised 47% iron oxide, 7% elemental carbon, 11% organic carbon, and 14% metallic and mineral oxides. Although a relationship between line depth and air quality inside the tube trains was evident, there were clear influences relating to the distance from cleaner outside air and the exchange with cabin air when the doors open. The passenger population-weighted exposure analysis demonstrated a method to identify stations that should be prioritised for remediation to improve air quality.ConclusionPM2.5 concentrations in the LU are many times higher than in other London transport Environments. Failure to include this environment in epidemiological studies of the relationship between PM2.5 and health in London is therefore likely to lead to a large exposure misclassification error. Given the significant contribution of underground PM2.5 to daily exposure, and the differences in composition compared to urban PM2.5, there is a clear need for well-designed studies to better understand the health effects of underground exposure.

Project description:BackgroundPrenatal exposure to fine particulate matter with a diameter of ≤2.5 μm (PM2.5) has been linked to adverse neurodevelopmental outcomes in later childhood, while research on early infant behavior remains sparse.ObjectivesWe examined associations between prenatal PM2.5 exposure and infant negative affectivity, a stable temperamental trait associated with longer-term behavioral and mental health outcomes. We also examined sex-specific effects.MethodsAnalyses included 559 mother-infant pairs enrolled in the PRogramming of Intergenerational Stress Mechanisms (PRISM) cohort. Daily PM2.5 exposure based on geocoded residential address during pregnancy was estimated using a satellite-based spatiotemporal model. Domains of negative affectivity (Sadness, Distress to Limitations, Fear, Falling Reactivity) were assessed using the Infant Behavior Questionnaire-Revised (IBQ-R) when infants were 6 months old. Subscale scores were calculated as the mean of item-specific responses; the global Negative Affectivity (NA) score was derived by averaging the mean of the four subscale scores. Bayesian distributed lag interaction models (BDLIMs) were used to identify sensitive windows for prenatal PM2.5 exposure on global NA and its subscales, and to examine effect modification by sex.ResultsMothers were primarily racial/ethnic minorities (38% Black, 37% Hispanic), 40% had ≤12 years of education; most did not smoke during pregnancy (87%). In the overall sample, BDLIMs revealed that increased PM2.5 at mid-pregnancy was associated with higher global NA, Sadness, and Fear scores, after adjusting for covariates (maternal age, education, race/ethnicity, sex). Among boys, increased PM2.5 at early pregnancy was associated with decreased Fear scores, while exposure during late pregnancy was associated with increased Fear scores (cumulative effect estimate = 0.57, 95% CI: 0.03-1.41). Among girls, increased PM2.5 during mid-pregnancy was associated with higher Fear scores (cumulative effect estimate = 0.82, 95% CI: 0.05-1.91).ConclusionsPrenatal PM2.5 exposure was associated with negative affectivity at age 6 months, and the sensitive windows may vary by subdomains and infant sex.

Dataset Information

Neuropathology changed by 3- and 6-months low-level PM_2.5 inhalation exposure in spontaneously hypertensive rats.

Background

Results

Conclusions

Publications

Neuropathology changed by 3- and 6-months low-level PM<sub>2.5</sub> inhalation exposure in spontaneously hypertensive rats.

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Dataset Information

Neuropathology changed by 3- and 6-months low-level PM2.5 inhalation exposure in spontaneously hypertensive rats.

Background

Results

Conclusions

Publications

Neuropathology changed by 3- and 6-months low-level PM<sub>2.5</sub> inhalation exposure in spontaneously hypertensive rats.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Neuropathology changed by 3- and 6-months low-level PM_2.5 inhalation exposure in spontaneously hypertensive rats.