Pre and post-natal exposure to ambient level of air pollution impairs memory of rats: The role of oxidative stress

Abstract and Figures

The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary objectives, it was to evaluate if the change of filtered to nonfiltered environment could protect the cortex of rats against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into four groups (n = 12/group): pre and post-natal exposure until adulthood to filtered air (FA); pre-natal period to nonfiltered air (NFA-FA); until (21st post-natal day) and post-natal to filtered air until adulthood (PND21); pre-natal to filtered air until PND21 and post-natal to nonfiltered air until adulthood (FA-NFA); pre and post-natal to nonfiltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a significant increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 +/- 0.217; NFA-FA: 1.101 +/- 0.217; FA-NFA: 1.014 +/- 0.300; NFA: 5.978 +/- 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group presented a significant decrease in short-term discriminative (FA: 0.603 +/- 0.106; NFA-FA: 0.669 +/- 0.0666; FA-NFA: 0.374 +/- 0.178; NFA: -0.00631 +/- 0.106 sec; p = 0.006) and an improvement in habituation memories when compared to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative memory and cortical oxidative stress may mediate this process.
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Air pollution is an emergent public health problem. Clinical
and pre-clinical studies indicate a positive correlation
between the levels of pollutants and human health damage
(Saldiva et al., 1994, 1995). Pre-natal exposure to air pollut-
ants induces low birthweight, decreases newborn height
and increases the risk of miscarriage in the rst 3 months of
pregnancy (Maroziene & Grazuleviciene, 2002; Dugandzic
et al., 2006; Hansen et al., 2008, Wang et al., 2009) Perera
et al. (2009) have demonstrated that continuous exposure of
pregnant women to aromatic polycyclic hydrocarbons caused
a decrease in their children intelligence quotient.
Recently, Calderón-Garcidueñas et al. (2008) demon-
strated that air pollution determines prefrontal cortex brain
inammation in children with sudden death (Calderón-
Garcidueñas et al., 2008a) or with signs of cognitive
impairment (Calderón-Garcidueñas et al., 2008a). Other
epidemiological studies have shown that the exposure to
environmental lead is an important risk factor for attention
decit hyperactivity disorder (Oberdörster et al., 2005b).
(Received 14 December 2009; revised 14 May 2010; accepted 16 May 2010)
ISSN 0895-8378 print/ISSN 1091-7691 online © 2010 Informa UK Ltd
DOI: 10.3109/08958378.2010.494313
Pre and post-natal exposure to ambient level of air
pollution impairs memory of rats: the role of oxidative
Ana C.T. Zanchi1,2, Lucas S. Fagundes2, Fernando Barbosa Jr.3, Rosane Bernardi4,
Claudia Ramos Rhoden2, Paulo H.N. Saldiva1, and Angela Cristina do Valle5
1Laboratory of Experimental Air Pollution. Department of Pathology, School of Medicine, University of São Paulo, São Paulo,
Brazil, 2Laboratory of Oxidative Stress and Atmospheric Pollution, Health Basic Sciences Department, Federal University
of Health Sciences of Porto Alegre (UFCSPA), Rio Grande do Sul, Brazil, 3Trace Elements Lab, Faculty of Pharmaceutical
Sciences of Ribeirão Preto, University of São Paulo (USP), Ribeirão Preto, Brazil,
Pharmacology Division, Basic Health Sciences
Department, Federal University of Health Sciences of Porto Alegre, (UFCSPA), Rio Grande do Sul, Brazil, and 5Neuroscience
Lab, School of Medicine, University of São Paulo, Brazil
The aims of this study were to evaluate whether air pollution during pre-natal and post-natal phases change
habituation and short-term discriminative memories and if oxidants are involved in this process. As secondary
objectives, it was to evaluate if the change of ltered to nonltered environment could protect the cortex of rats
against oxidative stress as well as to modify the behavior of these animals. Wistar, male rats were divided into
four groups (n = 12/group): pre and post-natal exposure until adulthood to ltered air (FA); pre-natal period to
nonltered air (NFA-FA); until (21st post-natal day) and post-natal to ltered air until adulthood (PND21); pre-
natal to ltered air until PND21 and post-natal to nonltered air until adulthood (FA-NFA); pre and post-natal to
nonltered air (NFA). After 150 days of air pollution exposure, animals were tested in the spontaneous object
recognition test to evaluate short-term discriminative and habituation memories. Rats were euthanized; blood
was collected for metal determination; cortex dissected for oxidative stress evaluation. There was a signicant
increase in malondialdehyde (MDA) levels in the NFA group when compared to other groups (FA: 1.730 ± 0.217;
NFA-FA: 1.101 ± 0.217; FA-NFA: 1.014 ± 0.300; NFA: 5.978 ± 1.920 nmol MDA/mg total proteins; p = 0.007). NFA group
presented a signicant decrease in short-term discriminative (FA: 0.603 ± 0.106; NFA-FA: 0.669 ± 0.0666; FA-NFA:
0.374 ± 0.178; NFA: −0.00631 ± 0.106 sec; p = 0.006) and an improvement in habituation memories when compared
to other groups. Therefore, exposure to air pollution during both those periods impairs short-term discriminative
memory and cortical oxidative stress may mediate this process.
Keywords: Air pollution; memory; oxidative stress
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14 May 2010
16 May 2010
© 2010 Informa UK Ltd
Address for Correspondence: Ana C.T. Zanchi, Rua Gonçalves Ledo, 129, Partenon, Porto Alegre, Rio Grande do Sul 90610-250, Brazil; E-mail:
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2 Ana C.T. Zanchi et al.
In an experimental study, Zanchi et al. (2008) have found
that the striatum and cerebellum of adult rats treated dur-
ing 1 month with toxic particles of residual oil y ash (ROFA)
by the respiratory route showed oxidative stress. ese ani-
mals also demonstrated a decreased motor activity, without
impairment of habituation when tested in the open-eld test
(Zanchi et al., 2010).
Some of nonessential toxic metals such as cadmium (Cd)
and lead (Pb) are absorbed by the surfaces of automotive
particulate matter (PM) of air pollution (Environmental
Protect Agency, 2006; Nordberg et al., 2007b). Exposure to
toxic metals during organogenesis may give rise to struc-
tural fetal anomalies, and exposure during other periods
of development may result in embryo or fetal lethality or
developmental impairment (Apostoli et al., 2007). Data on
the concentration of Cd in maternal blood, placental, and
fetal blood indicate that Cd accumulates in the placenta,
reaching the human fetus in detectable amounts (Nordberg
et al., 2007a, 2007b). Several studies in rats and mice dem-
onstrated Cd fetotoxicity and it is most often manifested as
reduced fetal weight and neurobehavioral toxicity (Nordberg
et al., 2007a).erefore, the eects produced by metals
depend on the timing and duration of exposure, on their
distribution and accumulation in various organs such as the
nervous system, and on the ability to interfere with specic
developmental processes (Apostoli et al., 2007; Nordberg
et al., 2007a, 2007b). Eects may be enhanced by biochemi-
cal, physiological and anatomical changes occurring during
development, which may result in a modied metabolism
of the metal (or trace element) itself (Apostoli et al., 2007).
Neurodevelopment impairment in humans secondary to
fetal exposure to Cd, Hg and Pb may range from serious
mental retardation and other overt clinical syndromes to
subclinical decits as sensory, motor, and cognitive impair-
ment (Apostoli et al., 2007).
Essential metals such as Se, Cu, Mn, and Zn are important
cofactors to the antioxidant enzyme system. Zinc (Zn) is a
cofactor for ZnCuSOD (Halliwell & Gutteridge, 1998) that
catalyzes the dismutation of superoxide anion to hydrogen
peroxide and oxygen. Selenium (Se) is a cofactor for CAT
(Halliwell & Gutteridge, 1998) and glutathione peroxidase
(GPx; Halliwell & Gutteridge, 1998). Both enzymes cata-
lyze the next step of this biochemical pathway by breaking
the hydrogen peroxide and generating water and oxygen
(Halliwell & Gutteridge, 1998).
e aim of this study was to investigate memory status
after air pollution exposure during pre-natal and early post-
natal phases and the role of oxidants in these parameters.
Materials and methods
Animal care
is study was approved by the review board for human
and experimental studies of the University of the São Paulo
School of Medicine (CAPPesq-0067/07) and by the Ethical
Committee for Research of the Federal University of Health
Sciences of Porto Alegre (CPA 084/03). e study was carried
out in accordance with international and national guidelines
for animal welfare (Goldim, 1995).
Male Wistar rats (n = 8), 45 days old, from the Biological
Research Institute Facility of Rio Grande do Sul, Brazil, were
hold in polluted or clean chambers up to 72 days old or one
spermatogenesis cycle. Females (n = 40) were from the same
facility and lived in nonltered (NFAC) or ltered (FAC) air
chambers during 15 days for adjustment to the environment
before mating. e animals were group housed in polypropyl-
ene cages (47 cm × 34 cm × 18 cm), six rats per cage, and main-
tained inside the polluted or clean chambers, in a temperature
(22° + 2°C) and light-controlled 12-h-light/dark cycles (light
from 7:00 a.m. to 7:00 p.m.) environment. Food (conventional
laboratory diet Supra-lab, Alisul Alimentos S.A., São Leopoldo,
RS, Brazil) and water were available ad libitum.
After the adjustment period, one male mated with ve
females for 13 days inside both chambers. Pregnancies were
conrmed by visual inspection and immediately after preg-
nant females were separated from males. Approximately,
18 females from FAC and 20 females from NFACs became
pregnant. During the gestational period, one female per cage
were left undisturbed. After delivery (1° day) we registered the
total number of alive and dead pups, the number of males
and females and the pups’ weight. Later, on the seventh day,
osprings were weighed again and their development was
monitored during the time of exposure in both chambers
by the emergence of fur and eye opening. Puppies from six
litters were weaned on the 21st post-natal day (PND21) and
separated by gender.
Site of exposure
e experiments were carried out in exposure chambers
located in the garden of the Federal University of Health
Sciences of Porto Alegre, south of Brazil, which is located on
a high trac density avenue where the source of air pollution
is predominantly automotive.
e 11.8 m3 exposure chambers were built on a metal-
lic structure and covered with a plastic ultraviolet protec-
tion lm. e air of each exposure chamber was supplied
by a ltration air unit at a ow rate of 33 l/min. e FAC
unit consisted of two pre-lters (PP-30 and pleat pre-lter
of 18), chemical (Puracarb® and PK-12; Borges–Katayama,
Sao Paulo, Brazil) and high eciency particulate arresting
(HEPA) lters stages (Pural® side access TAG B07-8338,
Borges–Katayama, Sao Paulo, Brazil). e PP-30 had a 30%
average eciency and the pleat pre-lter of 18, 60% of aver-
age eciency. ese pre-lters were mechanical barriers
to remove the dust and avoid obstruction of the surface of
the pores of pellets in the next stage of this unit. e next
stage consisted of Puracarb® (activated coal) and PK-12
in ‘V’ which is made from acrylonitrile butadiene styrene
plastic, that contains Pural® CHEMI SELECT (alumen
impregnated with potassium permanganate). Moreover,
there were two stages of HEPA PH-97 which had a 99.97%
highest eciency (Borges–Katayama, Sao Paulo, Brazil).
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Exposure to air pollution impairs memory 3
Puracarb® presents the neutralization capacity to H2S, SO2,
of 20%, 5%, and 8%, respectively and the Pural
SELECT, the neutralization capacity to H
, NO, and O
of 14%, 7%, 4.9%, and 90%, respectively (Borges–Katayama,
Sao Paulo, Brazil). e HEPA lters retain 99.97% of dust
and PM2.5, besides the microorganisms (Borges–Katayama,
Sao Paulo, Brazil). e NFAC presented only the mechanical
lter. Additionally, the pressure inside the chambers did not
exceed the atmospheric pressure by more than 3 cm H2O.
Approximately, 1960 l/h of air ow was provided by a fan
assembled between the ltration unit outlet and the cham-
ber inlet (Figure 1).
Pollutant determination
Air samples of each chamber were taken daily to meas-
ure PM2.5 concentrations during the exposure period. e
24-h concentration was determined gravimetrically (de
André, 2009) using Harvard impactor (Air Diagnostics and
Engineering Inc., Harrison, ME, 151, USA) at a ow rate of
10 l/min and equipped with polycarbonate lters. Results
were expressed as μg/m3. e total monthly PM2.5 mass from
February to June 2008 was determinate. During the exposure
period, humidity in Porto Alegre was between 50% and 95%
and temperature, between 10 and 25°C.
Experimental design
Male rats, PND21, from each group (ltered and nonltered)
were distributed into four experimental groups each one with
12 animals according to the following protocol: (1) pre and
post-natal exposure to FA until adulthood (FA); (2) pre-natal
until PND21 exposed to NFA and then to FA until adulthood
(NFA-FA); (3) pre-natal until PND21 exposed to FA and then
to NFA until adulthood (FA-NFA); (4) pre and post-natal
exposure to NFA (NFA). e animals were kept in plastic
cages (47 cm × 34 cm × 18 cm), six animals per cage at con-
trolled temperature (22° + 2°C), 12-h-light/dark cycles (light
from 7:00 a.m. to 7:00 p.m.), food (conventional laboratory
diet Supra-lab, Alisul Alimentos S.A., Brazil) and water were
available ad libitum. For the next 150 days (February to June
2008) the rats were exposed or not to air pollution 24 h daily
inside the chambers.
On the 151st day, the animals were submitted to the behav-
ioral test. After this test, they were euthanized by decapitation
and the troncular blood was collected in order to analyze toxic
and essential trace elements. e brain was removed, and all
cortex area was dissected, immediately frozen and stored in
an −80°C freezer for oxidative stress evaluation.
Spontaneous nonmatching-to-sample recognition test
e spontaneous nonmatching-to-sample recognition test
(SORT) was used because such paradigm allows investi-
gating discriminative memory and habituation (Aggleton
et al., 1997). In this context, the term discriminative memory
refers to the ability of discriminating between familiar and
nonfamiliar objects which could experimentally be repre-
sented as a form of episodic memory dependent on cortical
circuits (Aggleton et al., 1997). Habituation is quantied
by the dierence of time spent in exploring both objects
between sessions. is kind of memory is more automatic
and classied by some authors as a form of procedural
memory dependent on sub-cortical structures (Aggleton
et al., 1997).
e SORT was applied in a gray-painted wooden test
box (60 × 45 × 45 cm) which oor was covered with paper
that was removed between each session. Two sets of dier-
ent objects, heavy enough to prevent displacement, were
used. e behavioral procedure was always conducted from
9:00 a.m. to 1:00 p.m. On the rst day of test, the rats were
placed in the middle of the box without any objects for 3 min
(environmental habituation session) and then returned
to their home cages. Twenty-four hours later, the rats were
individually placed in the middle of the box, facing two
identical objects arranged in the opposite side and allowed
to explore them for 3 min and then returned to their cages.
Forty-ve minutes later, the rats were reintroduced into the
box for the test session where the objects had been replaced
Figure 1. Chambers structure. NFAC (nonltered air chamber); FAC (ltered air chamber).
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4 Ana C.T. Zanchi et al.
by one clean familiar object and one novel or nonfamiliar
object and the animals were allowed to explore both objects
for 3 min (Aggleton et al., 1997; Bernardi et al., 2004). e two
sessions were recorded in a DVD recorder. e videos were
analyzed by a blind trained observer through direct compu-
ter keyboard input BASIC-written software (Kevin Willioma,
KD Ware Computer, Boston, MA, USA, modied by omas
Sning the objects from a distance of less than 2 cm or
touching them with the nose were the behavioral parameters
used to determine the discrimination index. e discrimina-
tion index was calculated by the ratio between the dierence
of time exploring the novel and the familiar objects and the
total time spent exploring both objects during the choice
session (novel familiar/novel + familiar). Habituation to
the test environment was obtained by the dierence of time
sning both objects in the training session and in the test
session (Aggleton et al., 1997; Bernardi et al., 2004).
Oxidative stress analysis
Tissue preparation
Dissected cortex was homogenized in nine volumes of
120 mM KCl, 30 mM sodium phosphate buer (pH 7.2) added
with protein inhibitors (1 µg/ml leupeptin, 1 µg/ml aprotinin,
10 µg/ml soybean trypsin inhibitor, 1 µg/ml pepstatin, and
0.5 mM PMSF). e suspension was centrifuged at 600 g for
10 min at 0–4°C to remove nuclei and cell debris. e pellets
were discarded and the supernatants were used as homoge-
nates (Neves, 1997).
Determination of TBARS—lipid peroxidation
e determination of lipid peroxidation (LP) was performed
using the thiobarbituric acid reactive substances (TBARS)
method (Buege & Aust, 1978), as a measurement for oxida-
tive stress. Homogenates were precipitated with 10% trichlo-
roacetic acid, centrifuged, and incubated with TBA (Sigma
Chem. Co., St. Louis, MO, USA) for 15 min at 100°C. TBARS
were extracted using butanol (1:1; v/v). After centrifuga-
tion, the absorbance of the butanol layer was measured at
535 nm. e concentration of TBARS was expressed in nmol
malondialdehyde (MDA)/mg of total proteins (Buege & Aust,
1978; Neves, 1997). MDA standard was prepared from
tetramethoxypropane. Protein concentration was measured
using the Bradford Protein Assay at 595 nm (Schleicher &
Wieland, 1978) considering bovine serum albumin (1 mg/
ml) as standard.
Determination of superoxide dismutase
Superoxide dismutase (SOD) activity was performed accord-
ing to Marklund and Marklund (Marklund & Marklund,
1974). e reaction consists in inhibiting the pyrogallol
autoxidation by SOD activity. In a cuvet, 930 µl of 2-amino-2-
hydroxymethyl-propane-1,3-diol (TRIS) buer (TRIS 50 mM,
ethylenediaminetetraacetic acid 1 mM, pH 8.2), 4 µl of cata-
lase (CAT; 30 µM) and 50 µl of homogenate were added and
mixed. After, pyrogallol (24 mM in HCl 10 mM) was added and
SOD activity determined at 25°C at 420 nm in 60 and 120 sec.
One unit of SOD is dened as the quantity of enzyme that is
capable of inhibiting 50% of the reaction. e results were
expressed in Units of SOD/ mg total proteins.
Determination of CAT
CAT concentration was performed accordingly to Aebi
(1984). In a quartzo cuvet, 30 µl of homogenate, 2865 µl of
phosphate buer (50 mM, pH 7.4) were mixed. Afterwards,
105 µl of hydrogen peroxide (0.01 M) was added and mixed.
e decomposition of hydrogen peroxide by CAT activity was
determined at 25°C at 240 nm (ultraviolet) for 120 sec. e
results were expressed in pmol/mg of total proteins.
Total gluthatione
e total gluthatione (tGSH; glutathione reduced + glutath-
ione disulde) was assayed using an available glutathione kit
at 412 nm (Sigma CS0260, Saint Louis, MO, USA), following
Tietze (1969) the protocol. e measurement of tGSH consists
in a kinetic assay with catalytic amounts (nmoles) of GSH
causing a continuous reduction of 5, 5-dithiobis (2-nitroben-
zoic acid) to 5-thio-2-nitrobenzoic acid. e results were
expressed in nmol/mg of total proteins.
All measurements were carried out in a Perkin–Elmer
Lambda 35 spectrophotometer (Perkin–Elmer do Brasil, Sao
Paulo, Brazil).
Index of oxidative stress
e index of oxidative stress was calculated by the ([SOD]/
[CAT]) rate (Pinho et al., 2006).
Toxic and essential trace elements determination
Blood samples were analyzed for trace elements determi-
nation according to the method proposed by Batista et al.
(2009). Briey, 100 μl of blood were diluted 1:50 v/v in a solu-
tion containing 0.01% (v/v) Triton® X-100 (Sigma-Aldrich,
São Paulo, Brazil) and 0.05% (v/v) HNO
. After that, analysis
were carried out with an inductively coupled plasma mass
spectrophotometer equipped with a reaction cell (DRC-
ICP-MS ELAN DRC II; Perkin–Elmer, SCIEX, Norwalk, CT,
USA) operating with high purity argon (99.999%, Praxair,
Brazil) and ammonium as the reaction gas (99.999%.
Praxair, Rio de Janeiro, RJ, Brazil). Subsequent experiments
were performed in order to select the internal standard.
Rhodium (Rh), iridium (Ir) and Y (Yttrium) were evaluated
as internal standards. Rhodium (103) exhibited better or
equal performance compared to other internal standards,
regarding precision and accuracy for the determination
of arsenium (As), cadmium (Cd), cobalt (Co), chromium
(Cr), manganese (Mn), lead (Pb), selenium (Se), thalium
(Tl), vanadium (V) and iridium (193) for copper (Cu),
and zinc (Zn) determinations in blood reference samples
(QMEQAS07B03 and QMEQAS07B06). en, all blood sam-
ples and matrix-matching standards were prepared contain-
ing 10 µgl−1 Rh or Ir. Method detection limits for 114Cd, 63Cu,
55Mn, 208Pb, 82Se, and 64Zn were 3.0, 280, 9.0, 3.0, 264, 800 ng/l,
respectively. Results were expressed in μg/l blood (Batista
et al., 2009). Data validation was checked by the analysis
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Exposure to air pollution impairs memory 5
of trace elements in two blood certied reference materi-
als produced by the National Institutes of Standards and
Technology (SRM 955c trace elements in caprine blood and
SRM 966 trace elements in bovine blood) and by the analysis
of two reference materials produced by the Institut National
de Santé Publique du Québec, Centre de Toxicologie. Target
values and found values were in good agreement.
Statistical analysis
Results were expressed as mean ± standard error of the mean,
unless otherwise stated. Student t test was used to compare
pups development parameters between both chambers.
one way analysis of variance (ANOVA) followed by post-hoc
Student–Newman–Keuls test was used to compare values
of MDA, CAT, SOD, tGSH, [SOD]/[CAT], toxic and essential
trace elements blood concentrations and behavioral param-
eters among FA, NFA-FA, FA-NFA, and NFA groups. Two
way ANOVA followed by all pair wise multiple comparison
procedures (Student-Newman-Keuls test) was used to deter-
mine interaction between birth place until PND21 and the
change of environment after this period on habituation and
discrimination (novel object − familiar object/novel object +
familiar object ratio). All statistical analysis was performed
using Sigma-Stat 3.11 Software (Systat Software Inc. 2004,
Point Richmond, CA, USA). e level of signicance was set
at 5%.
e levels of oxidative stress were evaluated by the cortical
concentrations of MDA, SOD, CAT, and tGSH. A signicant
increase in MDA levels was found in the NFA group when
compared to FA, NFA-FA, and FA-NFA groups (p = 0.007;
Figure 2A). Accordingly, the index of oxidative stress was
lower in NFA when compared to NFA-FA group (p = 0.046)
(Figure 2B). A statistically signicant decrease in the tGSH
levels was found in the FA-NFA group when compared to FA,
NFA-FA, and FA-NFA groups (p = 0.003; Figure 2C).
e results of the SORT test are shown in Figure 3. e NFA
group showed a signicant decrease (p = 0.006) in the discrim-
ination index of objects when compared to FA, NFA-FA, and
FA-NFA groups (Figure 3A). e habituation was higher in the
NFA group when compared to FA, NFA-FA, and FA-NFA groups
rats from NFA group showed a signicant increase (p = 0.001)
in total exploration time of both objects in the training session
when compared to total exploration time in the test session
(habituation test; Figure 3B). In terms of habituation index,
there was a signicant interaction between the place of birth
and the change of environment (p = 0.035).
In Table 1, we presented the trace elements concentra-
tions determined by X-ray uorescence of samples col-
lected in Porto Alegre, 2008. e total monthly PM2.5 mass
during the exposure period (February to June, 2008) was
16.2 ± 5.8 µg/m3.
e results of toxic and essential trace elements blood
concentration were present in Table 2. [Cd] was higher in
FA-NFA and NFA when compared to FA group. [Cu], [Se], and
[Zn] presented higher concentrations in NFA-FA group when
compared to FA, NFA-FA, and FA-NFA groups.
In the current study, it was shown that pre and post-natal
(NFA; rst childhood) exposure to environmental air pollu-
tion (Table 1) induces an increase in cortex oxidative stress
(Figure 2A, 2B, and 2C) as well as an impairment of short-term
discriminative memory (Figure 3A), without macroscopically
impairment of developmental parameters.
[MDA] nmol/mg
total proteins
arbitrary units
[tGSH] nmol/mg
total proteins
Figure 2. Oxidative stress in cortex of rats exposed to ambient level of air
pollution. Groups: FA (ltered air chamber): pre and post-natal exposure
to ltered air ; NFA-FA (nonltered air-ltered air): pre-natal exposure
to nonltered air until 21st post-natal day (PND21) and then post-natal
exposure to ltered air until adulthood; FA-NFA (ltered air-nonltered
air): pre-natal exposure to ltered air until PND21 and then post-natal
exposure to nonltered air until adulthood; NFA (nonltered air): pre
and post-natal exposure to nonltered air. Values represent the mean
of 12 rats per group + SEM. (A) malondialdehyde (MDA) nmol/mg total
proteins, *p = 0.007; F(3; 26) = 5.219 when compared NFA to FA, NFA-FA
and FA-NAF groups; (B) [SOD]/[CAT] ratio, *p = 0.046 when compared
NFA-FA to NFA; (C) tGSH nmol/total proteins, *p = 0.003; F(3; 24) = 6.464
when compared FA-NFA to NFA to FA, NFA-FA and FA-NAF groups. CAT,
catalase; SOD, superoxide dismutase; tGSH, total gluthatione. SEM,
standard error of the mean.
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6 Ana C.T. Zanchi et al.
Oxidative stress is now recognized as potentially able to
trigger damages to multiple human and animal tissues. Brain
damage can occur during any stage of its development which
is demonstrated by a diversity of pathological manifestations
(Sunyer, 2008). Veras et al. (2008) have shown that the oxi-
dative stress generated by gestational exposure in mice to
particulate urban air pollution was associated with reduced
volumes, calibers, and surface areas of maternal placenta
blood spaces and increased fetal capillary surfaces and dif-
fuse conductance of toxic particles. Damasceno-Rodrigues
et al. (2009) have shown a positive interaction between pre
and post-natal exposure to air pollution with MDA levels in
mice heart, indicating that a reinforcement deleterious eects
of pollutants may occur on myocardial cells.
We found that post-natal (FA-NFA) and pre and post-natal
exposure (NFA) to air pollution determines signicant high
blood levels of Cd when compared to those animals never
exposed (FA) or exposed only during the pre-natal (NFA-FA)
up to PND21. On the other hand, the animals exposed to air
pollution in the pre-natal period and then moved into a non-
polluted environment (FA-NFA) presented signicant higher
blood concentration of Cu, Se and Zn. In rats treated with Cd
during pregnancy, lactation and for 8 weeks after weaning
(at doses ranging from 3, 5, 14 mg/Kg), there were behavio-
ral and neurotoxicological changes (Nordberg et al., 2007a).
Open-eld behavior and spontaneous and evoked cortical
activity were investigated in these same animals at the age
of 12 weeks (Nordberg et al., 2007a). Vertical exploration
activity and open-eld center exploration were increased;
spontaneous and evoked electrophysiological variables
showed dose-dependent and generation-dependent changes,
indicating that low level of inorganic Cd (3, 5, 14 mg/Kg)
can aect some nervous system functions (Nordberg et al.,
2007a, 2007b). Chow et al. (2008) (Chow et al., 2008) showed
the toxic properties of Cd in red blood cells during zebrash
embryonic brain development, in which Cd increased MDA
levels and induced neurotoxicity by impairing neurogenesis,
neuronal dierentiation, and axonogenesis. Cadmium is also
involved in apoptotic cell death of endothelial cells of blood
brain barrier (BBB) through the depletion of antioxidant sub-
stances and enhanced LP (Shukla et al., 1996). In the present
study, higher blood levels of Cd were found in the post-natal
group (FA-NFA) probably secondary to the inhalation of Cd
adsorbed in the PM surface until adult age. e signicant
high blood levels of Cd found in the NFA group reect the
combination of the direct exposure of primitive nervous tis-
sue to Cd at early stages of gestation before BBB is established
(Nordberg et al., 2007b). Takeda (2000) showed that BBB is
immature up to 2 weeks after birth in rats and 4 months in
humans, which allows the penetration of toxic substances
in the central nervous system (CNS). e inhalation of Cd
adsorbed in the PM surface could also challenge the integrity
of the BBB and the CNS by an immunological mechanism
secondary to systemic inammation (Oberdörster et al.,
Table 1. Trace elements concentrations determined by X-ray uorescence
of samples collected in polycarbonate lters in Porto Alegre, 2008.
Trace elements Concentration (ng/m3 air)
Mg 40.5 ± 28.8
Al 39.9 ± 33.0
Si 75.2 ± 94.9
P 5.8 ± 6.3
S 383.4 ± 355.8
CI 54.5 ± 113.7
K 227.4 ± 266.5
Ca 36.1 ± 35.7
Ti 3.9 ± 4.2
V 0.7 ± 0.8
Cr 1.0 ± 2.2
Mn 2.8 ± 3.3
Fe 63.9 ± 63.3
Co —
Ni 0.7 ± 1.6
Cu 2.6 ± 4.0
Zn 14.9 ± 19.5
Se 1.4 ± 1.1
Br 2.4 ± 2.4
Pb 5.8 ± 5.5
Values were expressed as mean ± standard error of the mean.
36 × 34 mm (300 × 300 DPI).
Index of discrimination (s)
Habituation index (s)
Figure 3. Indexes of short-term discriminative memory and habituation
of rats exposed to ambient level of air pollution. Groups : FA (ltered air
chamber): pre and post-natal exposure to ltered air; NFA-FA (nonltered
air-ltered air): pre-natal exposure to nonltered air until 21st post-natal
day (PND21) and then post-natal exposure to ltered air until adulthood;
FA-NFA (ltered air-nonltered air): pre-natal exposure to ltered air until
PND21 and then post-natal exposure to nonltered air until adulthood;
NFA (nonltered air): pre and post-natal exposure to nonltered air. Values
represent the mean of 12 rats per group + SEM. (A) shows a signicant
increase of the habituation index (s) in the group NFA when compared
NFA to FA NFA-FA and FA-NFA, *p = 0.001; F(3; 30) = 4.197; (B) shows a
signicant reduction of the discrimination index (s) in the group NFA
when compared NFA to FA NFA-FA and FA-NFA,*p = 0.006; F(3; 23) = 5.479;
**shows the interaction between place of birth of rats and the change of
environment after PND21 (p = 0.035). SEM, standard error of the mean.
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Exposure to air pollution impairs memory 7
2005a, 2005b). Another mechanism of Cd deleterious eects
could be given by modication of essential metals metabolic
pathways like the production of an inactive form of CuZnSOD
by displacement Zn of its site in this enzyme (Chater et al.,
2008). Cadmium also interacts with Se and disrupts GPx
activity (Chater et al., 2008). In addition, Cd could displace
Fe and Cu from storing proteins as ferritin and ceruplasmin
determining an increase of reactive oxygen species (ROS)
through Fenton reaction (Fe+2 or Cu+1 reduced reacts with
hydrogen peroxide which results in hydroxyl radical and Fe or
Cu oxidized—Fe+3 or Cu+2; Halliwell & Gutteridge, 1998). e
bioavailability of Cd to tissues is reduced through conjugation
with mellathionin and storage (Chater et al., 2008; Nordberg
et al., 2007a, 2007b). Cadmium is also excreted by the bile
but this process utilizes GSH and depletes the antioxidant
system (Quig, 1998). erefore, animals from FA-NFA group
presented a decrease in GSHt concentration, which was
probably because GSH consumption during Cd excretion by
On the other hand, humans and animals utilize an anti-
oxidant defense system to neutralize the biological oxidative
damage and protect the organs by scavenging the ROS. is
system is composed of the enzymes CAT, Cu-Zn and Mn
SODs (CuZnSOD and MnSOD) and GPx as well as nonen-
zymatic substances like reduced glutathione (GSH; Hussain
et al., 1995). Our results demonstrated that FA-NFA and NFA
groups presented an increase of Cd concentration. e NFA
group presented cortical lipoperoxidation, which was dem-
onstrated by a signicant increase in MDA levels (Figure 2A).
e oxidative index is the ration between [SOD] and [CAT]
(Pinho et al., 2006). NFA group presented signicant decrease
in oxidative stress index (Figure 2B). e SOD concentration
in this group was lower than CAT. ereby, there was an
excess of superoxide anion, which reacts with biomolecules
like proteins, lipids, and DNA (Halliwell & Gutteridge, 1998).
e oxidative index demonstrated an excess of cortical NFA
group CAT concentration to detoxied H
. As consequence
of the higher concentration of H
from cellular metabolism,
there was an increase in tGSH because of higher activity of
GPx (Figure 2C) (Halliwell & Gutteridge, 1998). On the other
hand, NFA-FA group presented higher concentrations of Cu,
Se, and Zn, which improve the antioxidant system of these
animals. Khan and Black (2003) have demonstrated that rat
brain protein levels of GSH, CuZnSOD, MnSOD, total SOD
as well as GPx and CAT activity increase at the end of ges-
tation and in newborns up to PND21 (post-natal day 21).
ese developmental-induced modications are parallel to
the metabolic demand and to free radical generation during
myelination and synaptogenesis, which occur at around the
PND10–14 days in the mouse brain (Khan & Black, 2003).
Nevertheless, some studies related a decrease of antioxidant
endogenous system responses with aging (Lahiri et al., 2007)
exacerbated by the interaction of aging and restraint stress
(Chakraborti et al., 2008).
ere are increasing evidences showing that the CNS
is a target of air pollution induced damage (Calderón-
Garcidueñas et al., 2008a, 2008b; Suglia et al., 2008).
Recently, it has been demonstrated that chronic ROFA
instillation promoted LP in striatum and cerebellum of
adult rats. is damage was protected by n-acetylcysteine
(NAC) treatment (Zanchi et al., 2008). It has also been veri-
ed that ROFA instillation decreased the motor activity of
rats and that NAC did not reverse this eect (Zanchi et al.,
2008). After that we intended to study the memory state of
animals exposed to air pollutants in dierent life periods
and to correlate our ndings with biochemical oxidative
stress parameters. We utilized the SORT that was originally
described as a working memory test (Ennaceur & Delacour,
1988) but also modied to study mutant mice, aging decits,
early developmental inuences, nootropic manipulations,
teratological drug exposure, and novelty seeking (Bevins
& Besheer, 2006). e ndings related to the evaluation of
memory by SORT corroborate the idea that the exposure to
air pollution adversely modies some of the brain functions.
Table 2. Toxic and essential trace elements blood concentration of rats
exposed to ambient level of air pollution.
Trace elements Groups Concentration (µg/l) p
Cd FA 0.13 ± 0.052 0.005
= 5.870
NFA-FA 0.22 ± 0.098
FA-NFA 0.29 ± 0.075*
NFA 0.28 ± 0.066*
Pb FA 1.98 ± 1.11 0.496
= 5.823
NFA-FA 2.65 ± 2.21
FA-NFA 3.82 ± 3.02
NFA 2.65 ± 1.29
Cu FA 927.83 ± 145.07 0.002
= 7.416
NFA-FA 1148.50 ± 89.23*
FA-NFA 1002.83 ± 90.42
NFA 908.67 ± 34.50
Mn FA 13.63 ± 4.88 0.104
= 2.345
NFA-FA 15.50 ± 5.24
FA-NFA 9.87 ± 2.27
NFA 9.77 ± 5.15
Se FA 407.33 ± 74.17 0.001
= 7.904
NFA-FA 535.33 ± 17.32*
FA-NFA 449.17 ± 61.65
NFA 404.33 ± 40.47
Zn FA 5674.83 ± 720.52 0.001
= 7.715
NFA-FA 7145.00 ± 268.27*
FA-NFA 6274.50 ± 664.33
NFA 5958.50 ± 478.80
Values were expressed as mean ± standard error of the mean.
ANOVA one way followed by Student Newman Keuls to compare FA ,
NFA-FA, FA-NFA, NFA: [Cd]: *signicant dierence between FA-NFA
and FA groups; [Pb]: *signicant dierence between NAF and FA groups.
[Cu]: *signicant dierence between NFAFA and FA-NFA; NFA-FA and FA;
NFA-FA and NFA groups ; [Se]: *signicant dierence between NFA-FA and
FA-NFA; NFA-FA and FA; NFA-FA and NFA groups; [Zn]: *signicant dif-
ference between NFA-FA and FA-NFA; NFA-FA and FA; NFA-FA and NFA
53 × 43 mm (300 × 300 DPI).
FA, pre and post-natal exposure until adulthood to ltered air; FA-NFA,
post-natal to nonltered air until adulthood; NFA, pre and post-natal to
nonltered air; NFA-FA, pre-natal period to nonltered air.
Inhalation Toxicology Downloaded from by on 06/22/10
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8 Ana C.T. Zanchi et al.
A signicant impairment of the short-term discriminative
memory was seen only in the NFA group, suggesting that
the exposure to air pollution during all the animal lifetime
determined a signicant impairment of short-term discrimi-
native memory. Animals exposed during only pre (NFA-FA)
or post-natal (FA-NFA) period did not show impairment of
this kind of memory. e continuous exposure to a polluted
environment could predispose the animals to neuronal
damage induced by oxidative stress like described above
and similarly to what happens in the myocardial cells
(Damaceno-Rodrigues et al., 2009). On the other hand,
there was a clear opposite eect of the exposure to air pol-
lution on the habituation parameters. e habituation index
was higher in animals exposed to air pollution in both pre
and post-natal (NFA) periods until adulthood and of those
exposed only after PND21 (FA-NFA). ese data suggest that
early and continuous exposure to pollutants trigger some
mechanisms involved in potentializing the adaptation
ability to novel environments. An interaction between the
place of birth of rats and the change of rats was observed,
which conrms that the change of environment from FAC
to NFAC may also improve habituation capacity. e results
from this research are in agreement with the idea that the
mechanisms involved in the modulation of discriminative
memory and habituation are dissimilar as are the sensibility
of these systems to oxidative stress damage (Salomons et al.,
2010). Nevertheless, Zanchi et al. (2010) have shown that
adult rats which were exposed to ROFA for 30 days did not
change habituation parameters evaluated by open-eld test.
Since habituation can occur with an unlimited number of
behavioral responses, this diversity hinders the establish-
ment of a single mechanism or CNS anatomical site and
the apparent conicting results may be explained by the
dierent paradigms employed in both studies.
In summary, the data showed that exposure to ambient
level of air pollution during pre and post-natal period (NFA
group) impairs the short-term discriminative memory, and
suggests that gestational and rst childhood periods are the
key for these eects. Furthermore, cortical oxidative stress
may have an important role to mediate the impairment of
short-term discriminative memory induced by urban pol-
lutants. e improved habituation secondary to air pollu-
tion exposure suggests that those behaviors in which the
mechanisms require more primitive physiological, anatomi-
cal, and cellular processes may be potentiated in response
to environmental adversity. is preliminary study opened
a myriad of questions that demands further studies for
e authors would like to thank Dr. Elia Caldini, MSc. Nilsa
Damaceno Rodrigues (Cell Biology Laboratory, Medical
School, University of São Paulo); Dr. Mariangela Macchione,
Dr. Mariana Matera Veras (Laboratory of Experimental
Pollution, University of São Paulo). Lucas Sagrillo Fagundes,
Lucianna Schmitt, Marcella Ody Piva, Maria Fernanda
Hornos Carneiro, Roberto Marques Damiani (Laboratory
of Oxidative Stress and Atmospheric Pollution, Basic Health
Sciences Department, Federal University of Health Sciences
of Porto Alegre, Rio Grande do Sul, Brazil) for their technical
Declaration of interest
is work was supported by University of São Paulo, Federal
University of Health Sciences of Porto Alegre, Fundação
de Amparo a Pesquisa do Estado de São Paulo (FAPESP)
and FINEP. A.C. Zanchi is supported by a fellowship from
FAPESP, Dr. P.H.N. Saldiva and Dr. C.R. Rhoden supported
by—Conselho Nacional de Desenvolvimento Cientíco e
Tecnológico—CNPq. Dr. P.H.N. Saldiva and Dr. A.C. Valle
are support by FAPESP. e authors declare that there are no
conicts of interest.
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... In a previous study, we showed that the pre plus post-natal exposure of rats to environmental AP induced an impairment of discriminative memory with preservation of environment habituation memory (Zanchi et al. 2010a). Habituation memory is usually considered to be a consequence of the action of a procedural learning brain system that involves the striatum and connected basal ganglia. ...
... All the above procedures are detailed elsewhere (Zanchi et al. 2008(Zanchi et al. , 2010a(Zanchi et al. , 2010bDamaceno-Rodrigues et al. 2009;Fagundes et al. 2015). ...
... Finally, considering the importance of striatum for procedural or non-declarative memory (Rankin et al. 2009;Squire and Dede 2015), the studies that evaluate habituation memory can give information about the functional state of striatum. Zanchi et al. (2010a) found a progressive decrease in object exploration determined by chronic exposure to AP that could be representative of increased levels of habituation. Woodward et al. (2017) studied the impact of intermittent exposure of female mice to nPM from ambient urban traffic emissions in several parameters as neuritic atrophy, white matter degeneration, and microglial activation. ...
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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.
... In an animal study, it was found that exposure to ambient air pollution both pre-and postnatally induced shortterm memory deficit as assessed by the novel object recognition test in offspring, indicating that the exposure to PM2.5-enriched air leads to cognitive impairment [51]. Young adult mice that inhaled PM2.5 for 10 months showed impairment in spatial learning and memory [52]. ...
... Increasing lines of evidence from epidemiological and experimental studies have found increased levels of cytokines, inducible nitric oxide synthase, and COX-2 in human brains [15], human cerebrospinal fluid [83], and experimental animal brains [15,63,84] accompanied with impaired cognitive function which is associated with the level of PM. The affected brain regions include the olfactory bulb [24], cortex [51,85,86], hippocampus [87], and striatum [76]. ...
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The increasing amount of particulate matter (PM) in the ambient air is a pressing public health issue globally. Epidemiological studies involving data from millions of patients or volunteers have associated PM with increased risk of dementia and Alzheimer’s disease in the elderly and cognitive dysfunction and neurodegenerative pathology across all age groups, suggesting that PM may be a risk factor for neurodegenerative diseases. Neurodegenerative diseases affect an increasing population in this aging society, putting a heavy burden on economics and family. Therefore, understanding the mechanism by which PM contributes to neurodegeneration is essential to develop effective interventions. Evidence in human and animal studies suggested that PM induced neurodenegerative-like pathology including neurotoxicity, neuroinflammation, oxidative stress, and damage in blood–brain barrier and neurovascular units, which may contribute to the increased risk of neurodegeneration. Interestingly, antagonizing oxidative stress alleviated the neurotoxicity of PM, which may underlie the essential role of oxidative stress in PM’s potential effect in neurodegeneration. This review summarized up-to-date epidemiological and experimental studies on the pathogenic role of PM in neurodegenerative diseases and discussed the possible underlying mechanisms.
... Several in vitro studies have also shown a buildup of Aβ plaques as an effect of increased neuronal and glial beta-secretase (BACE) expression involved in promoting the amyloidogenic pathway of APP processing, which was correlated with a concomitant increase in the COX-1 and COX-2 protein levels and a modest alteration in the cytokine profile (Bhatt et al., 2015). In addition to neuroinflammatory states, microglia and astrocytes, which are brain resident immune cells, are involved in the metabolism and clearance of Aβ (Griffin et al., 1998;Nagele et al., 2004;Heppner et al., 2015). in vitro and in vivo research carried out thus far indicates that PM exposure is involved in inflammatory processes (Campbell et al., 2005), oxidative stress (Calderón-Garcidueñas et al., 2004;Zanchi et al., 2010), amyloidogenesis (Calderón-Garcidueñas et al., 2004, 2010Levesque et al., 2011;Cacciottolo et al., 2017), and the negative impacts on behavior in animals (Allen et al., 2014b), but much more work involving AD animal models is needed to determine if and how PM exposure could alter AD and other dementias. ...
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Air pollution is regarded as an important risk factor for many diseases that affect a large proportion of the human population. To date, accumulating reports have noted that particulate matter (PM) is closely associated with the course of cardiopulmonary disorders. As the incidence of Alzheimer’s disease (AD), Parkinson’s disease (PD), and autoimmune disorders have risen and as the world’s population is aging, there is an increasing interest in environmental health hazards, mainly air pollution, which has been slightly overlooked as one of many plausible detrimental stimuli contributing to neurodegenerative disease onset and progression. Epidemiological studies have indicated a noticeable association between exposure to PM and neurotoxicity, which has been gradually confirmed by in vivo and in vitro studies. After entering the body directly through the olfactory epithelium or indirectly by passing through the respiratory system into the circulatory system, air pollutants are subsequently able to reach the brain. Among the potential mechanisms underlying particle-induced detrimental effects in the periphery and the central nervous system (CNS), increased oxidative stress, inflammation, mitochondrial dysfunction, microglial activation, disturbance of protein homeostasis, and ultimately, neuronal death are often postulated and concomitantly coincide with the main pathomechanisms of neurodegenerative processes. Other complementary mechanisms by which PM could mediate neurotoxicity and contribute to neurodegeneration remain unconfirmed. Furthermore, the question of how strong and proven air pollutants are as substantial adverse factors for neurodegenerative disease etiologies remains unsolved. This review highlights research advances regarding the issue of PM with an emphasis on neurodegeneration markers, symptoms, and mechanisms by which air pollutants could mediate damage in the CNS. Poor air quality and insufficient knowledge regarding its toxicity justify conducting scientific investigations to understand the biological impact of PM in the context of various types of neurodegeneration.
... Developmental studies with Wistar male rats exposed to PM 2.5 who were assessed for short term memory performance using spontaneous nonmatching to sample recognition tests analogous to novel object recognition, demonstrated significant reductions in discrimination and less exploration time of novel objects after 150 days of exposure. The authors identified a potential underlying mechanism being cortical oxidative stressors, as they reported increases in Malondialdehyde (MDA) [41]. Using adult Sprague-Dawley male rats (2 months old), it was demonstrated that intra-tracheal injection of PM 2.5 for up to a year damaged sensory functions as well as learning and memory as a function of ultrastructural changes in mitochondria and neuronal myelin sheaths, along with abnormal expression of apoptosisrelated proteins (Caspase-3, Caspase-9) [42]. ...
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An estimated 92% of the world’s population live in regions where people are regularly exposed to high levels of anthropogenic air pollution. Historically, research on the effects of air pollution have focused extensively on cardiovascular and pulmonary health. However, emerging evidence from animal and human studies has suggested that chronic exposures to air pollution detrimentally change the functioning of the central nervous system with the result being proteinopathy, neurocognitive impairment, and neurodegenerative disease. Case analyses of aging World Trade Center responders suggests that a single severe exposure may also induce a neuropathologic response. The goal of this report was to explore the neuroscientific support for the hypothesis that inhaled particulate matter might cause an Alzheimer’s-like neurodegenerative disease, in order to consider proposed mechanisms and latency periods linking inhaled particulate matter and neurodegeneration, and to propose new directions in this line of research.
... Wistar rats Reduced SOD and MDA in animals treated both pre and postnatally. tGSH [35] reduced in PND21 to adulthood group only. Reduced performance in spontaneous nonmatching-to-sample recognition test for continuous exposure and PND21 to adulthood. ...
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Emerging evidence is showing that air pollution is a chronic source of neuroinflammation, which has a causal relationship with Alzheimer 's disease (AD), an increasingly common and devastating illness in elderly populations. A report on the association between PM from air pollution and AD provided scientific explanations for the mechanisms driving air pollution-induced CNS pathology, which stimulates calls for action at the political level. This scoping review considers the range of recognised and novel approaches associated with AD, highlighting how neu-robiology, sociology of medicine and eco-politics collaborate to generate the interdisciplinary picture of the effects of PM on this malignancy. Such holistic approaches will allow this field to move forward and could lead to an improvement of actionable policies.
... Ambient air pollution has long been recognized as a worldwide environmental and public health threat [1], and the cardiovascular and respiratory effects of air pollution have been well documented [2]. Furthermore, there is also growing evidence of its adverse effect on neurodevelopment [3,4]. Recently, both animal-and population-based epidemiological studies have reported neurodevelopmental deficits in children related to maternal exposure to air pollution during pregnancy [5][6][7][8]. ...
... More specifically, studies report elevated levels of in systemic inflammatory markers, neuro-inflammatory markers or neurodegenerative pathologies after exposure to high levels of air pollution (Calderon-Garciduenas et al., 2008Gruzieva et al., 2017;Levesque, Surace, et al., 2011). Experimental PM exposures are reported to provoke astrocyte and microglial activation, triggering inflammation, and disturbing redox signaling leading to neurotoxicity (Allen, Liu, Pelkowski, et al., 2014;Allen, Liu, Weston, et al., 2014;Block et al., 2004;Onoda et al., 2017a, b;Zanchi et al., 2010). Epidemiological research has further identified airborne PM as one of the environmental factors potentially involved in Alzheimer's disease and Parkinson's disease pathogenesis, with redox responses and neuroinflammation as possible key players (for review, see (Heusinkveld et al., 2016). ...
While the impact of emissions from combustion of fossil fuel on human health has been extensively studied, current knowledge of exhaust exposure from combustion of biofuels provides limited and inconsistent information about its neurotoxicity. The objective of the present work was to compare the gene expression patterns in rat frontal cortex and hippocampus after exposure to diesel exhaust emissions (DEE) from combustion of two 1st generation fuels, 7% fatty acid methyl esters (FAME) (B7) and 20% FAME (B20), and a 2nd generation 20% FAME/hydrotreated vegetable oil (SHB20: synthetic hydrocarbon biofuel), with and without diesel particulate filter (DPF). The Fisher 344 rats (n = 7/treatment) were exposed to DEE for 7 days (6h/day), and for 28 days (6h/day, 5 days/week) in whole body exposure chambers. The controls were breathing room air. Brain histological examinations did not reveal any adverse exposure-related effects of DEE in frontal cortex or in hippocampus. Gene expression analysis showed that several genes associated with antioxidant defenses and inflammation were statistically differently expressed in DEE exposed animals versus control. In addition, the gene expression changes between the exposure groups were compared, where the observed rank order in frontal cortex was B7 > B20 > SHB20 after 7 days of exposure, and SHB20 > B7 = B20 after 28 days of exposure. In the hippocampus, the rank order was B7 > SHB20 > B20. Effect of DPF treatment was observed for Tnf only. Overall, moderate increases in bio-components in diesel blends do not appear to result in dramatic alterations in gene expression or adverse histopathological effects.
... If exposure to pollutants occurs early in life, as likely to occur in populations residing near pollution sources, developmental effects might permanently alter stress physiology and cognitive ability (Koller et al., 2004;Baos et al., 2006), with correlated effects on personality traits (Baugh et al., 2012(Baugh et al., , 2017Van Oers and Naguib, 2013;Griffin et al., 2015). Indeed, in an experimental study, pre-and postnatal exposure of rats to toxic pollutants caused oxidative stress and memory deficits as indicated by impairments in object recognition, which could cause increased fearfulness towards objects that are encountered with relative rarity (Zanchi et al., 2010). On the other hand, there are also studies that suggest limited effects of metal exposure on traits related to risk sensitivity. ...
Animal personalities, as defined by repeatable among individual differences in behavior, can vary across urbanization gradients. However, how urbanization affects personalities remains incompletely understood, especially because different urban stressors could affect personality traits in opposing ways, whereas most previous studies have considered only one urban disturbance factor. For instance, novel habitat features could favor reduced neophobia, whereas exposure to pollutants could increase risk sensitivity through neurotoxic or hormonal effects. To address this contingency, we studied object neophobia in four urban populations of great tits (Parus major) that vary in exposure to metal pollution and anthropogenic disturbance, as quantified by proximity to roads and pathways. We measured the return latency of incubating females when flushed from the nest and presented with up to two different novel objects, allowing quantification of behavioral repeatability and plasticity. To separate neophobia from sensitivity to disturbance, we also conducted baseline trials, in which females were flushed but no object was presented. We additionally measured exploration behavior and aggression (hissing) during nest defense, to explore whether suites of behaviors covary with urbanization, and examined whether neophobia affects reproductive success. Sensitivity to disturbance and neophobia were repeatable, and thus represent personality traits. Moreover, females occupying territories near roads and pathways had shorter return latencies during novel object but not baseline trials, suggesting a specific reduction in neophobia in disturbed areas. Plasticity in neophobia also increased with disturbance level. In contrast, metal exposure did not affect neophobia or sensitivity to disturbance, despite negatively correlating with exploration behavior. Neophobia correlated with exploration behavior, but not aggression or reproductive success. Results suggest that shifts in personality types in urbanized areas might involve specific reductions in neophobia, rather than general reductions in sensitivity to disturbance, and unexpectedly indicate no effect of toxic metals on risk sensitivity.
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Epidemiological studies consistently implicate traffic-related air pollution (TRAP) and/or proximity to heavily trafficked roads as risk factors for developmental delays and neurodevelopmental disorders (NDDs); however, there are limited preclinical data demonstrating a causal relationship. To test the effects of TRAP, pregnant rat dams were transported to a vivarium adjacent to a major freeway tunnel system in northern California where they were exposed to TRAP drawn directly from the face of the tunnel or filtered air (FA). Offspring remained housed under the exposure condition into which they were born and were tested in a variety of behavioral assays between postnatal day 4 and 50. To assess the effects of near roadway exposure, offspring of dams housed in a standard research vivarium were tested at the laboratory. An additional group of dams was transported halfway to the facility and then back to the laboratory to control for the effect of potential transport stress. Near roadway exposure delayed growth and development of psychomotor reflexes and elicited abnormal activity in open field locomotion. Near roadway exposure also reduced isolation-induced 40-kHz pup ultrasonic vocalizations, with the TRAP group having the lowest number of call emissions. TRAP affected some components of social communication, evidenced by reduced neonatal pup ultrasonic calling and altered juvenile reciprocal social interactions. These findings confirm that living in close proximity to highly trafficked roadways during early life alters neurodevelopment.
Every second we inhale a danger in the air; many particles in the atmosphere can influence our lives. Outdoor air pollution, especially particulate matter is the largest environmental risk factor and has been associated with many cardiovascular and lung diseases. Importantly, air pollution has recently been discovered to also impact the brain. Here, we review the effects of air pollution on glial cells of the brain, astrocytes and microglia, and the tightly controlled interplay between these cell types. We focus on how traffic related air pollutants which include both gaseous and particulate emissions and their secondary products influence the intercellular communication of microglia and astrocytes. Finally, we place these air pollution and glial interactions in a larger context by discussing their impact on neurodegeneration.
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Human exposures to metals and metalloids such as arsenic frequently occur as mixtures, and hence it is important to consider interactions among these elements in terms of both mechanisms of action ...
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Exposure to air pollution can elicit cardiovascular health effects. Children and unborn fetuses appear to be particularly vulnerable. However, the mechanisms involved in cardiovascular damage are poorly understood. It has been suggested that the oxidative stress generated by air pollution exposure triggers tissue injury. To investigate whether prenatal exposure can enhance oxidative stress in myocardium of adult animals, mice were placed in a clean chamber (CC, filtered urban air) and in a polluted chamber (PC, São Paulo city) during the gestational period and/or for 3 mo after birth, according to 4 protocols: control group-prenatal and postnatal life in CC; prenatal group-prenatal in PC and postnatal life in CC; postnatal group-prenatal in CC and postnatal life in PC; and pre-post group-prenatal and postnatal life in PC. As an indicator of oxidative stress, levels of lipid peroxidation in hearts were measured by malondialdehyde (MDA) quantification and by quantification of the myocardial immunoreactivity for 15-F2t-isoprostane. Ultrastructural studies were performed to detect cellular alterations related to oxidative stress. Concentration of MDA was significantly increased in postnatal (2.45 +/- 0.84 nmol/mg) and pre-post groups (3.84 +/- 1.39 nmol/mg) compared to the control group (0.31 +/- 0.10 nmol/mg) (p < .01). MDA values in the pre-post group were significantly increased compared to the prenatal group (0.71 +/- 0.15 nmol/mg) (p = .017). Myocardial isoprostane area fraction in the pre-post group was increased compared to other groups (p </= .01). Results show that ambient levels of air pollution elicit cardiac oxidative stress in adult mice, and that gestational exposure may enhance this effect.
Handbook of the Toxicology of Metals is the standard reference work for physicians, toxicologists and engineers in the field of environmental and occupational health. This new edition is a comprehensive review of the effects on biological systems from metallic elements and their compounds. An entirely new structure and illustrations represent the vast array of advancements made since the last edition. Special emphasis has been placed on the toxic effects in humans with chapters on the diagnosis, treatment and prevention of metal poisoning. This up-to-date reference provides easy access to a broad range of basic toxicological data and also gives a general introduction to the toxicology of metallic compounds. * Covers up-to-date toxicological information on 31 metallic elements and their compounds, each in a separate chapter * New chapters on general chemistry, biological monitoring and biomarkers, essential metals, principles for prevention of the toxic effects of metals, and more.
1. Oxygen is a toxic gas - an introductionto oxygen toxicity and reactive species 2. The chemistry of free radicals and related 'reactive species' 3. Antioxidant defences Endogenous and Diet Derived 4. Cellular responses to oxidative stress: adaptation, damage, repair, senescence and death 5. Measurement of reactive species 6. Reactive species can pose special problems needing special solutions. Some examples. 7. Reactive species can be useful some more examples 8. Reactive species can be poisonous: their role in toxicology 9. Reactive species and disease: fact, fiction or filibuster? 10. Ageing, nutrition, disease, and therapy: A role for antioxidants?