676
Introduction
he link between elevated concentrations of air pollution
and adverse public health efects is now well established.
Increased levels of particulate matter (PM10 and PM2.5)
are widely recognized for their causal contribution to
mortality and cardiovascular morbidity and mortality
(Pope et al., 2009; Brook et al., 2010). Important legislative
eforts have been made in most industrialized countries
to reduce emissions of pollutants and to determine safe
levels. Although it remains unclear which pollutants or
fraction of particles are driving the health efects that are
identiied in epidemiological studies, strong circumstan-
tial evidence indicates that traic plays an important role.
In addition, evidence is accumulating that
exposure to air pollution can cause brain damage and
neurodegeneration. Long-term exposure to air pollution
is associated with neuroinlammation and a disruption
of the blood-brain barrier (Calderón-Garcidueñas
RESEARCH ARTICLE
Changed gene expression in brains of mice exposed
to traic in a highway tunnel
Inge Bos
1,2
, Patrick De Boever
1,3
, Jan Emmerechts
4,5
, Jurgen Buekers
1
, Jeroen Vanoirbeek
5
,
Romain Meeusen
2
, Martine Van Poppel
1
, Benoit Nemery
5
, Tim Nawrot
3,5
, and Luc Int Panis
1,6
1
Flemish Institute for Technological Research (VITO), Mol, Belgium,
2
Department of Human Physiology & Sports
Medicine, Vrije Universiteit Brussel, Brussels, Belgium,
3
Centre for Environmental studies (CMK), Hasselt University,
Diepenbeek, Belgium,
4
Center for Molecular and Vascular Biology, University of Leuven, Belgium,
5
Department of
Public Health, Occupational and Environmental Medicine, Unit of Lung Toxicology, University of Leuven, Leuven,
Belgium, and
6
Transportation Research Institute (IMOB), Hasselt University, Diepenbeek, Belgium
Abstract
Context: Air pollution has been suggested to have an impact on the brain.
Objective: The objective was to assess the expression of inlammation-related genes in the brains of mice that had
been exposed for 5 days to a well-characterized traic-polluted environment, i.e. a highway tunnel.
Materials and methods: Twenty C57BL6 mice were randomly allocated to four groups of ive animals. Two groups were
placed in the tunnel for 5 days (mean PM 2.5, 55.1 μg/m
3
, mean elemental carbon, EC 13.9 μg/m
3
) in cages with or
without ilter, two control groups were housed outside the tunnel. Animals were assessed within 24 hours after the
last exposure day. Lung injury and inlammation were assessed by bronchoalveolar lavage (BAL) and histology. Blood
leukocytosis and coagulation parameters were determined in peripheral blood. The olfactory bulb and hippocampus
were analyzed for changes in expression of inlammatory genes and brain-derived neurotrophic factor (BDNF).
Results and discussion: Although carbon particles were abundant in alveolar macrophages of exposed mice and
absent in non-exposed mice, there was no evidence of pulmonary or systemic inlammation. There was an increased
expression of genes involved in inlammatory response (COX2, NOS2, NOS3, and NFE2L2) in the hippocampus of the
exposed mice. In the olfactory bulb, a downregulation was found for IL1α, COX2, NFE2L2, IL6, and BDNF.
Conclusion: Although this short-term exposure to traic-related pollution did not induce pulmonary or systemic
inlammation, the expression of inlammatory genes was afected in diferent brain areas. The decreased BDNF
expression in the olfactory bulb suggests lower brain neurotrophic support in response to traic-related air pollution.
Keywords: Particulate matter, black carbon, brain-derived neurotrophic factor (BDNF), inlammation,
hippocampus, olfactory bulb, blood, bronchoalveolar lavage (BAL), lung
Address for Correspondence: Luc Int Panis, VITO, Environment and Health, Boeretang 200, 2400 Mol, Belgium. Tel: +32 14 335102.
Fax: +32 14 58 26 57. E-mail: luc.intpanis@vito.be
(Received 31 May 2012; revised 11 July 2012; accepted 17 July 2012)
Inhalation Toxicology, 2012; 24(10): 676–686
© 2012 Informa Healthcare USA, Inc.
ISSN 0895-8378 print/ISSN 1091-7691 online
DOI: 10.3109/08958378.2012.714004
Inhalation Toxicology Downloaded from informahealthcare.com by Vito on 08/21/12
For personal use only.