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      Effect of prolonged exposure to diesel engine exhaust on proinflammatory markers in different regions of the rat brain

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          Abstract

          Background

          The etiology and progression of neurodegenerative disorders depends on the interactions between a variety of factors including: aging, environmental exposures, and genetic susceptibility factors. Enhancement of proinflammatory events appears to be a common link in different neurological impairments, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, and multiple sclerosis. Studies have shown a link between exposure to particulate matter (PM), present in air pollution, and enhancement of central nervous system proinflammatory markers. In the present study, the association between exposure to air pollution (AP), derived from a specific source (diesel engine), and neuroinflammation was investigated. To elucidate whether specific regions of the brain are more susceptible to exposure to diesel-derived AP, various loci of the brain were separately analyzed. Rats were exposed for 6 hrs a day, 5 days a week, for 4 weeks to diesel engine exhaust (DEE) using a nose-only exposure chamber. The day after the final exposure, the brain was dissected into the following regions: cerebellum, frontal cortex, hippocampus, olfactory bulb and tubercles, and the striatum.

          Results

          Baseline levels of the pro-inflammatory cytokines tumor necrosis factor alpha (TNF-α) and interleukin-1 alpha (IL-1α) were dependent on the region analyzed and increased in the striatum after exposure to DEE. In addition, baseline level of activation of the transcription factors (NF-κB) and (AP-1) was also region dependent but the levels were not significantly altered after exposure to DEE. A similar, though not significant, trend was seen with the mRNA expression levels of TNF-α and TNF Receptor-subtype I (TNF-RI).

          Conclusions

          Our results indicate that different brain regions may be uniquely responsive to changes induced by exposure to DEE. This study once more underscores the role of neuroinflammation in response to ambient air pollution, however, it is valuable to assess if and to what extent the observed changes may impact the normal function and cellular integrity of unique brain regions.

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          Most cited references32

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          Adverse cardiovascular effects of air pollution.

          Air pollution is increasingly recognized as an important and modifiable determinant of cardiovascular disease in urban communities. Acute exposure has been linked to a range of adverse cardiovascular events including hospital admissions with angina, myocardial infarction, and heart failure. Long-term exposure increases an individual's lifetime risk of death from coronary heart disease. The main arbiter of these adverse health effects seems to be combustion-derived nanoparticles that incorporate reactive organic and transition metal components. Inhalation of this particulate matter leads to pulmonary inflammation with secondary systemic effects or, after translocation from the lung into the circulation, to direct toxic cardiovascular effects. Through the induction of cellular oxidative stress and proinflammatory pathways, particulate matter augments the development and progression of atherosclerosis via detrimental effects on platelets, vascular tissue, and the myocardium. These effects seem to underpin the atherothrombotic consequences of acute and chronic exposure to air pollution. An increased understanding of the mediators and mechanisms of these processes is necessary if we are to develop strategies to protect individuals at risk and reduce the effect of air pollution on cardiovascular disease.
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            Tumor necrosis factor-alpha (TNF-alpha) increases both in the brain and in the cerebrospinal fluid from parkinsonian patients.

            Tumor necrosis factor-alpha (TNF-alpha), a glial-cell-related factor, was measured for the first time in the brain (striatum) and cerebrospinal fluid (CSF) from control and parkinsonian patients by a sensitive sandwich enzyme immunoassay. The concentrations of TNF-alpha in the brain and CSF were significantly higher in parkinsonian patients than those in controls. Since TNF-alpha is an important signal transducer of the immune system with cytotoxic and stimulator properties, these results suggest that an immune response may occur in the nigrostriatal dopaminergic regions in Parkinson's disease and that TNF-alpha may be related, at least in part, to the neuronal degeneration.
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              Brain inflammation and Alzheimer's-like pathology in individuals exposed to severe air pollution.

              Air pollution is a complex mixture of gases (e.g., ozone), particulate matter, and organic compounds present in outdoor and indoor air. Dogs exposed to severe air pollution exhibit chronic inflammation and acceleration of Alzheimer's-like pathology, suggesting that the brain is adversely affected by pollutants. We investigated whether residency in cities with high levels of air pollution is associated with human brain inflammation. Expression of cyclooxygenase-2 (COX2), an inflammatory mediator, and accumulation of the 42-amino acid form of beta-amyloid (Abeta42), a cause of neuronal dysfunction, were measured in autopsy brain tissues of cognitively and neurologically intact lifelong residents of cities having low (n:9) or high (n:10) levels of air pollution. Genomic DNA apurinic/apyrimidinic sites, nuclear factor-kappaB activation and apolipoprotein E genotype were also evaluated. Residents of cities with severe air pollution had significantly higher COX2 expression in frontal cortex and hippocampus and greater neuronal and astrocytic accumulation of Abeta42 compared to residents in low air pollution cities. Increased COX2 expression and Abeta42 accumulation were also observed in the olfactory bulb. These findings suggest that exposure to severe air pollution is associated with brain inflammation and Abeta42 accumulation, two causes of neuronal dysfunction that precede the appearance of neuritic plaques and neurofibrillary tangles, hallmarks of Alzheimer's disease.
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                Author and article information

                Journal
                Part Fibre Toxicol
                Particle and Fibre Toxicology
                BioMed Central
                1743-8977
                2010
                17 May 2010
                : 7
                : 12
                Affiliations
                [1 ]Centre for Environmental Health, National Institute for Public Health and the Environment (RIVM), Bilthoven, the Netherlands
                [2 ]Institut für umweltmedizinische Forschung (IUF) at the Heinrich-Heine-University, Düsseldorf, Germany
                [3 ]Pharmaceutical Sciences, College of Pharmacy, Western University of Health Sciences, 309 E. Second Street, Pomona, California 91766-1854, USA
                Article
                1743-8977-7-12
                10.1186/1743-8977-7-12
                2883965
                20478040
                374f9c75-dfe5-4bf5-927b-b363b5df6379
                Copyright ©2010 Gerlofs-Nijland et al; licensee BioMed Central Ltd.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 27 January 2010
                : 17 May 2010
                Categories
                Research

                Toxicology
                Toxicology

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