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The impact of chronic exposure to air pollution over oxidative stress parameters and brain histology

Authors:
Rosane Bernardi at Universidade Federal de Ciências da Saúde de Porto Alegre
Rosane Bernardi
Ana C T Zanchi at University of São Paulo
Ana C T Zanchi
Nilsa Regina Damaceno-Rodrigues at University of São Paulo
Nilsa Regina Damaceno-Rodrigues
Mariana Matera Veras at Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo
Mariana Matera Veras
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Abstract and Figures

Air pollution (AP) triggers neuroinflammation and lipoperoxidation involved in physiopathology of several neurodegenerative diseases. Our study aims to investigate the effect of chronic exposure to ambient AP in oxidative stress (OS) parameters and number of neurons and microglial cells of the cortex and striatum. Seventy-two male Wistar rats were distributed in four groups of exposure: control group (FA), exposed throughout life to filtered air; group PA-FA, pre-natal exposed to polluted air until weaning and then to filtered air; group FA-PA, pre-natal exposed to filtered air until weaning and then to polluted air; and group PA, exposed throughout life to polluted air. After 150 days of exposure, the rats were euthanized for biochemical and histological determinations. The malondialdehyde concentration in the cortex and striatum was significantly higher in the PA group. The activity of superoxide dismutase was significantly decreased in the cortex of all groups exposed to AP while activity of catalase was not modified in the cortex or striatum. The total glutathione concentration was lower in the cortex and higher in the striatum of the FA-PA group. The number of neurons or microglia in the striatum did not differ between FA and PA. On the other hand, neurons and microglia cell numbers were significantly higher in the cortex of the FA-PA group. Our findings suggest that the striatum and cortex have dissimilar thresholds to react to AP exposure and different adaptable responses to chronically AP-induced OS. At least for the cortex, changing to a non-polluted ambient early in life was able to avoid and/or reverse the OS, although some alterations in enzymatic antioxidant system may be permanent. As a result, it is important to clarify the effects of AP in the cortical organization and function because of limited capacity of brain tissue to deal with threatening environments.
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RESEARCH ARTICLE
The impact of chronic exposure to air pollution over oxidative stress
parameters and brain histology
Rosane Bossle Bernardi
1,2,3
&Ana Cláudia Tedesco Zanchi
4
&Nilsa Regina Damaceno-Rodrigues
5
&
Mariana Matera Veras
4
&Paulo Hilário Nascimento Saldiva
4,6
&Helena Maria Tannhauser Barros
2,3
&
Cláudia Ramos Rhoden
1,2,3
Received: 16 December 2020 /Accepted: 16 April 2021
#The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021
Abstract
Air pollution (AP) triggers neuroinflammation and lipoperoxidation involved in physiopathology of several neurodegenerative
diseases. Our study aims to investigate the effect of chronic exposure to ambient AP in oxidative stress (OS) parameters and
number of neurons and microglial cells of the cortex and striatum. Seventy-two male Wistar rats were distributed in four groups
of exposure: control group (FA), exposed throughout life to filtered air; group PA-FA, pre-natal exposed to polluted air until
weaning and then to filtered air; group FA-PA, pre-natal exposed to filtered air until weaning and then to polluted air; and group
PA, exposed throughout life to polluted air. After 150 days of exposure, the rats were euthanized for biochemical and histological
determinations. The malondialdehyde concentration in the cortex and striatum was significantly higher in the PA group. The
activity of superoxide dismutase was significantly decreased in the cortex of all groups exposed to AP while activity of catalase
was not modified in the cortex or striatum. The total glutathione concentration was lower in the cortex and higher in the striatum
of the FA-PA group. The number of neurons or microglia in the striatum did not differ between FA and PA. On the other hand,
neurons and microglia cell numbers were significantly higher in the cortex of the FA-PA group. Our findings suggest that the
striatum and cortex have dissimilar thresholds to react to AP exposure and different adaptable responses to chronically AP-
induced OS. At least for the cortex, changing to a non-polluted ambient early in life was able to avoid and/or reverse the OS,
although some alterations in enzymatic antioxidant system may be permanent. As a result, it is important to clarify the effects of
AP in the cortical organization and function because of limited capacity of brain tissue to deal with threatening environments.
Keywords Air pollution .Oxidative stress .Brain histology
Introduction
Recently, Di et al. (2017) demonstrated by overwhelming
evidence the impact of air pollution (AP) in mortality of an
open cohort with 460,310,521 person-years of follow-up.
These authors showed that even low levels of chronic expo-
sure to PM
2.5
and ozone according to the National Ambient
Air Quality Standard (NAAQS) were associated with an in-
creased risk of death predominantly among black men and
people with low income. The strength of the evidence justifies
the permanent searching for methods to control and turn off
the AP poisonous effects.
The first evidence of the toxic effects of AP to the central
nervous system (CNS) was demonstrated by Zhang et al.
(1988). These authors found an increased risk of stroke in a
cohort of people exposed to indoor coal fumes. Afterward,
other authors (Hong et al. 2002; Lisabeth et al. 2008)
Responsible Editor: Lotfi Aleya
*Rosane Bossle Bernardi
bernardi@ufcspa.edu.br
1
Laboratory of OS and Atmospheric Pollution, Health Basic Sciences
Department, Federal University of Health Sciences of Porto Alegre
(UFCSPA), Porto Alegre, RS, Brazil
2
Post-Graduate Course in Health Sciences, Federal University of
Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, RS, Brazil
3
Pharmacology Division, Basic Health Sciences Department, Federal
University of Health Sciences of Porto Alegre (UFCSPA), Porto
Alegre, RS, Brazil
4
Laboratory of Experimental Air Pollution, Department of Pathology,
School of Medicine, University of São Paulo, São Paulo, SP, Brazil
5
Laboratory of Cellular Biology, School of Medicine, University of
São Paulo, São Paulo, SP, Brazil
6
Post-Graduate Course in Physiopathology, School of Medicine,
University of São Paulo, São Paulo, SP, Brazil
https://doi.org/10.1007/s11356-021-14023-0
/ Published online: 23 April 2021
Environmental Science and Pollution Research (2021) 28:47407–47417
Content courtesy of Springer Nature, terms of use apply. Rights reserved.
... Regarding in vivo evidence, in a recent study by Bernardi et al., the effects of chronic exposure to ambient air pollution on oxidative stress parameters and the number of neurons and microglial cells in the cortex and striatum of male Wistar rats were investigated [91]. The results showed that the concentration of malondialdehyde, a marker of lipid peroxidation, was significantly higher in the group exposed to air pollution throughout life. ...
... The results showed that the concentration of malondialdehyde, a marker of lipid peroxidation, was significantly higher in the group exposed to air pollution throughout life. Additionally, the activity of the antioxidant enzyme superoxide dismutase was significantly reduced in the cortex of all air pollution-exposed groups [91]. In a study conducted in northern Italy, Milani et al. assessed the impact of UFPs on different brain regions in male BALB/c mice [92]. ...
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Air pollution, a growing concern for public health, has been linked to various respiratory and cardiovascular diseases. Emerging evidence also suggests a link between exposure to air pollutants and neurodegenerative diseases, particularly Alzheimer’s disease (AD). This review explores the composition and sources of air pollutants, including particulate matter, gases, persistent organic pollutants, and heavy metals. The pathophysiology of AD is briefly discussed, highlighting the role of beta-amyloid plaques, neurofibrillary tangles, and genetic factors. This article also examines how air pollutants reach the brain and exert their detrimental effects, delving into the neurotoxicity of air pollutants. The molecular mechanisms linking air pollution to neurodegeneration are explored in detail, focusing on oxidative stress, neuroinflammation, and protein aggregation. Preclinical studies, including in vitro experiments and animal models, provide evidence for the direct effects of pollutants on neuronal cells, glial cells, and the blood–brain barrier. Epidemiological studies have reported associations between exposure to air pollution and an increased risk of AD and cognitive decline. The growing body of evidence supporting air pollution as a modifiable risk factor for AD underscores the importance of considering environmental factors in the etiology and progression of neurodegenerative diseases, in the face of worsening global air quality.
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... Oxidative stress (OS) is a state of oxidative imbalance caused by the production of reactive oxygen species (ROS) and reactive nitrogen species (RNS) that goes beyond antioxidant defense mechanisms (Fai et al., 2004) . The activity of SOD, MDA, GPX, and CAT enzymes is an indicator for showing the level of OS (Bernardi et al., 2021). An increase in the level of ROS or a reduction in the action of antioxidants, as well as incomplete removal of ROS in the cells, causes serious diseases and also can lead to the dysfunction of normal brain cells (Bernardi et al., 2021), and it has an important role in PM 2.5 -induced neurotoxicity and neuronal impairments (Wei et al., 2017). ...
... The activity of SOD, MDA, GPX, and CAT enzymes is an indicator for showing the level of OS (Bernardi et al., 2021). An increase in the level of ROS or a reduction in the action of antioxidants, as well as incomplete removal of ROS in the cells, causes serious diseases and also can lead to the dysfunction of normal brain cells (Bernardi et al., 2021), and it has an important role in PM 2.5 -induced neurotoxicity and neuronal impairments (Wei et al., 2017). ...
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... AAP exposure did not significantly alter the lipid profiles of the groups in our investigation. As in the report of Bernardi et al (26), the present study's AAP group had higher levels of SOD and TAC than the control group. ...
Air Pollution, Ozone, and Sulfur Dioxide Can Affect the Blood Serum Lipid Profile and Oxidative Stress of Male Wistar Rats
Article
Full-text available
  • May 2024
The majority of the body’s organs are impacted by ambient air pollution (AAP), which is currently a serious environmental global health issue. The objective of this work was to assess the impact of ozone (O3 ), sulfur dioxide (SO2 ), and AAP on oxidative stress (OS) and lipid profile indicators in male Wistar rats. To this end, these rats were exposed for three hours each day for five weeks in control, AAP, O3 (0.6 ppm), and SO2 (10 ppm) groups (each containing 8 animals). Several parameters, such as total antioxidant capacity (TAC), superoxide dismutase (SOD), glutathione peroxidase (GPx) activities, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), triglyceride, and malondialdehyde (MDA), were measured on blood samples. AAP exposure on TAC (P=0.014) and SOD (P=0.05), MDA (P=0.018), and HDL (P=0.003), O3 exposure on TAC (P<0.001), and SO2 exposure on blood serum TAC (P=0.006) all had statistically significant effects. Based on the results, exposure to SO2 and AAP did not significantly alter the lipid profile (P>0.05). According to our research, exposure to O3 , SO2 , and AAP can increase overall antioxidant capacity by stimulating blood serum oxidative defense enzymes. Except for the enhanced effect of O3 exposure on serum HDL, AAP, SO2 , and O3 exposures had no discernible effects on the lipid profile.
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... Preclinical models have revealed certain alterations in the central nervous system. In particular, alterations in cell proliferation, synaptogenesis, and brain development have been found with higher exposure to air pollution (Klocke et al., 2018a;Coburn et al., 2018;Zheng et al., 2019;Zhang et al., 2018), as well as changes in oxidative stress (Bernardi et al., 2021). In utero exposure to air pollution is related to microbleeds (Woodward et al., 2018) and morphological changes in the hippocampus (HCC; Ehsanifar et al., 2019), with alterations in certain neurotransmitter systems (Yokota et al., 2016a;Suzuki et al., 2010) and changes in brain development (Zheng et al., 2019;Klocke et al., 2018b). ...
Neurodevelopmental consequences of gestational exposure to particulate matter 10: Ultrasonic vocalizations and gene expression analysis using a bayesian approach
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  • Oct 2023
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Air pollution has been associated with a wide range of health issues, particularly regarding cardio-respiratory diseases. Increasing evidence suggests a potential link between gestational exposure to environmental pollutants and neurodevelopmental disorders such as autism spectrum disorder. The respiratory pathway is the most commonly used exposure model regarding PM due to valid and logical reasons. However, PM deposition on food (vegetables, fruits, cereals, etc.) and water has been previously described. Although this justifies the need of unforced, oral models of exposure, preclinical studies using oral exposure are uncommon. Specifically, air pollution can modify normal brain development at genetic, cellular, and structural levels. The present work aimed to investigate the effects of oral gestational exposure to particulate matter (PM) on ultrasonic vocalizations (USV). To this end, pregnant rats were exposed to particulate matter during gestation. The body weight of the pups was monitored until the day of recording the USVs. The results revealed that the exposed group emitted more USV calls when compared to the control group. Furthermore, the calls from the exposed group were longer in duration and started earlier than those from the non-exposed group. Gene expression analyses showed that PM exposure down-regulates the expression of Gabrg2 and Maoa genes in the brain, but no effect was detected on glutamate or other neurotransmission systems. These findings suggest that gestational exposure to PM10 may be related to social deficits or other phenomena that can be analyzed with USV. In addition, we were able to detect abnormalities in the expression of genes related to different neurotransmitter systems, such as the GABAergic and monoaminergic systems. Further research is needed to fully understand the possible effects of air pollutant exposure on neurodevelopmental disorders as well as the way in which these effects are linked to differences in neurotransmission systems.
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... As recent reviews suggested (Braithwaite et al., 2019;Lu, 2020), exposure to air pollution affects the risk of mental disorders by inducing oxidative stress and systemic inflammation (Arias-Perez et al., 2020), changing brain structure (Bernardi et al., 2021), and increasing stress hormone production (Li et al., 2017). However, anxiety-specific studies reported ambiguous PM 2.5 effects, with some showing null associations (Pelgrims et al., 2021;Shi et al., 2020;Vert et al., 2017). ...
Daily space-time activities, multiple environmental exposures, and anxiety symptoms: A cross-sectional mobile phone-based sensing study
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Full-text available
  • Apr 2022
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Several epidemiological studies have shown associations between developmental exposure to traffic-related air pollution and increased risk for autism spectrum disorders (ASD), a spectrum of neurodevelopmental disorders with increasing prevalence rate in the United States. Though animal studies have provided support for these associations, little is known regarding possible underlying mechanisms. In a previous study we found that exposure of C57BL/6J mice of both sexes to environmentally relevant levels (250–300 µg/m³) of diesel exhaust (DE) from embryonic day 0 to postnatal day 21 (E0 to PND21) caused significant changes in all three characteristic behavioral domains of ASD in the offspring. In the present study we investigated a potential mechanistic pathway that may be of relevance for ASD-like changes associated with developmental DE exposure. Using the same DE exposure protocol (250–300 µg/m³ DE from E0 to PND21) several molecular markers were examined in the brains of male and female mice at PND3, 21, and 60. Exposure to DE as above increased levels of interleukin-6 (IL-6) in placenta and in neonatal brain. The JAK2/STAT3 pathway, a target for IL-6, was activated by STAT3 phosphorylation, and the expression of DNA methyltransferase 1 (DNMT1), a STAT3 target gene, was increased in DE-exposed neonatal brain. DNMT1 has been reported to down-regulate expression of reelin (RELN), an extracellular matrix glycoprotein important in regulating the processes of neuronal migration. RELN is considered an important modulator for ASD, since there are several polymorphisms in this gene linked to the disease, and since lower levels of RELN have been reported in brains of ASD patients. We observed decreased RELN expression in brains of the DE-exposed mice at PND3. Since disorganized patches in the prefrontal cortex have been reported in ASD patients and disrupted cortical organization has been found in RELN-deficient mice, we also assessed cortical organization, by labeling cells expressing the lamina-specific-markers RELN and calretinin. In DE-exposed mice we found increased cell density in deeper cortex (lamina layers VI–IV) for cells expressing either RELN or calretinin. These findings demonstrate that developmental DE exposure is associated with subtle disorganization of the cerebral cortex at PND60, and suggest a pathway involving IL-6, STAT3, and DNMT1 leading to downregulation of RELN expression that could be contributing to this long-lasting disruption in cortical laminar organization.
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Background: The association between exposure to air pollutants and mental disorders among adults has been suggested, although results are not consistent. Objective: To analyze the association between long-term exposure to air pollution and history of anxiety and depression disorders and of medication use (benzodiazepines and antidepressants) in adults living in Barcelona. Methods: A total of 958 adults (45-74 years old) residents in Barcelona, most of them having at least one of their parents diagnosed with dementia (86%), and participating in the ALFA (Alzheimer and Families) study, were included. We used Land Use Regression (LUR) models to estimate long-term residential exposure (period 2009-2014) to PM2.5, PM2.5 absorbance (PM2.5 abs), PM10, PM coarse, NO2 and NOx. Between 2013 and 2014 participants self-reported their history of anxiety and depression disorders and related medication use. The analysis was focused on those participants reporting outcome occurrence from 2009 onwards (until 2014). Results: We observed an increased odds of history of depression disorders with increasing concentrations of all air pollutants [e.g. an increased odds of depression of 2.00 (95% CI; 1.37, 2.93) for each 10μg/m(3) NO2 increase]. Such associations were consistent with an increased odds of medication use in relation to higher concentrations of air pollutants [e.g. an increased odds of antidepressants use of 1.23 (1.04, 1.44) for each 20μg/m(3) NOx increase]. Associations regarding anxiety disorders did not reach statistical significance. Conclusions: Our study shows that increasing long-term exposure to air pollution may increase the odds of depression and the use of antidepressants and benzodiazepines. Further studies are needed to replicate our results and confirm this association.
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Article
  • Jun 2017
Background Studies have shown that long-term exposure to air pollution increases mortality. However, evidence is limited for air-pollution levels below the most recent National Ambient Air Quality Standards. Previous studies involved predominantly urban populations and did not have the statistical power to estimate the health effects in underrepresented groups. Methods We constructed an open cohort of all Medicare beneficiaries (60,925,443 persons) in the continental United States from the years 2000 through 2012, with 460,310,521 person-years of follow-up. Annual averages of fine particulate matter (particles with a mass median aerodynamic diameter of less than 2.5 μm [PM2.5]) and ozone were estimated according to the ZIP Code of residence for each enrollee with the use of previously validated prediction models. We estimated the risk of death associated with exposure to increases of 10 μg per cubic meter for PM2.5 and 10 parts per billion (ppb) for ozone using a two-pollutant Cox proportional-hazards model that controlled for demographic characteristics, Medicaid eligibility, and area-level covariates. Results Increases of 10 μg per cubic meter in PM2.5 and of 10 ppb in ozone were associated with increases in all-cause mortality of 7.3% (95% confidence interval [CI], 7.1 to 7.5) and 1.1% (95% CI, 1.0 to 1.2), respectively. When the analysis was restricted to person-years with exposure to PM2.5 of less than 12 μg per cubic meter and ozone of less than 50 ppb, the same increases in PM2.5 and ozone were associated with increases in the risk of death of 13.6% (95% CI, 13.1 to 14.1) and 1.0% (95% CI, 0.9 to 1.1), respectively. For PM2.5, the risk of death among men, blacks, and people with Medicaid eligibility was higher than that in the rest of the population. Conclusions In the entire Medicare population, there was significant evidence of adverse effects related to exposure to PM2.5 and ozone at concentrations below current national standards. This effect was most pronounced among self-identified racial minorities and people with low income. (Supported by the Health Effects Institute and others.)
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The Association Between Air Pollution and Onset of Depression Among Middle-Aged and Older Women
Article
  • Mar 2017
Despite recently reported associations between air pollution and acute psychiatric outcomes, the association with depression onset has not, to our knowledge, been previously examined. We conducted a prospective cohort study among 41,844 women in the Nurses' Health Study, in the United States. The women had an average age?of 66.6 (standard deviation, 7.6) years, were depression-free in 1996, and were followed through 2008. May-September ozone exposures were predicted by interpolating concentrations from the 5 nearest monitors. One-, 2-, and 5-year average concentrations of particulate matter with an aerodynamic diameter less than or equal to 2.5 ?m (PM2.5) were predicted at each participant's residence using a spatiotemporal model. We defined depression as report of doctor's diagnosis or use of antidepressant medication. We estimated adjusted hazard ratios with time-varying Cox models. Hazard ratios for both pollutants were elevated (per 10-parts-per-billion increase in ozone, hazard ratio (HR)?=?1.06; 95% confidence interval (CI): 1.00, 1.12; per 10-?g/m3 increase in 1-year PM2.5, HR?=?1.08; 95% CI: 0.97, 1.20). Associations were stronger when only antidepressant use was used to define cases (for ozone, HR?=?1.08; 95% CI: 1.02, 1.14; for PM2.5, HR?=?1.12; 95% CI: 1.00, 1.25). To our knowledge, these results represent the first identification of a possible association between both long-term ozone and PM2.5 exposure and depression onset. Although the stronger association specifically with antidepressant use may reflect that this endpoint better captures the onset time and milder cases, our findings should be interpreted with caution.
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