Dataset Information

Limited developmental neurotoxicity from neonatal inhalation exposure to diesel exhaust particles in C57BL/6 mice.

ABSTRACT:

Background

Recent epidemiological studies indicate early-life exposure to pollution particulate is associated with adverse neurodevelopmental outcomes. The need is arising to evaluate the risks conferred by individual components and sources of air pollution to provide a framework for the regulation of the most relevant components for public health protection. Previous studies in rodent models have shown diesel particulate matter has neurotoxic potential and could be a health concern for neurodevelopment. The present study shows an evaluation of pathological and protracted behavioral alterations following neonatal exposure to aerosolized diesel exhaust particles (NIST SRM 1650b). The particular behavioral focus was on temporal control learning, a broad and fundamental cognitive domain in which reward delivery is contingent on a fixed interval schedule. For this purpose, C57BL/6?J mice were exposed to aerosolized NIST SRM 1650b, a well-characterized diesel particulate material, from postnatal days 4-7 and 10-13, for four hours per day. Pathological features, including glial fibrillary-acidic protein, myelin basic protein expression in the corpus callosum, and ventriculomegaly, as well as learning alterations were measured to determine the extent to which NIST SRM 1650b would induce developmental neurotoxicity.

Results

Twenty-four hours following exposure significant increases in glial-fibrillary acidic protein (GFAP) in the corpus callosum and cortex of exposed male mice were present. Additionally, the body weights of juvenile and early adult diesel particle exposed males were lower than controls, although the difference was not statistically significant. No treatment-related differences in males or females on overall locomotor activity or temporal learning during adulthood were observed in response to diesel particulate exposure.

Conclusion

While some sex and regional-specific pathological alterations in GFAP immunoreactivity suggestive of an inflammatory reaction to SRM 1650b were observed, the lack of protracted behavioral and pathological deficits suggests further clarity is needed on the developmental effects of diesel emissions prior to enacting regulatory guidelines.

SUBMITTER: Morris-Schaffer K

PROVIDER: S-EPMC6322252 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Limited developmental neurotoxicity from neonatal inhalation exposure to diesel exhaust particles in C57BL/6 mice.

Morris-Schaffer Keith K Merrill Alyssa K AK Wong Candace C Jew Katrina K Sobolewski Marissa M Cory-Slechta Deborah A DA

Particle and fibre toxicology 20190107 1

<h4>Background</h4>Recent epidemiological studies indicate early-life exposure to pollution particulate is associated with adverse neurodevelopmental outcomes. The need is arising to evaluate the risks conferred by individual components and sources of air pollution to provide a framework for the regulation of the most relevant components for public health protection. Previous studies in rodent models have shown diesel particulate matter has neurotoxic potential and could be a health concern for ...[more]

PMID: 30612575

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Project description:BACKGROUND:Recent epidemiological studies indicate early-life exposure to air pollution is associated with adverse neurodevelopmental outcomes. Previous studies investigating neonatal exposure to ambient fine and ultrafine particles have shown sex specific inflammation-linked pathological changes and protracted learning deficits. A potential contributor to the adverse phenotypes from developmental exposure to particulate matter observed in previous studies may be elemental carbon, a well-known contributor to pollution particulate. The present study is an evaluation of pathological and protracted behavioral alterations in adulthood following subacute neonatal exposure to ultrafine elemental carbon. C57BL/6J mice were exposed to ultrafine elemental carbon at 50??g/m3 from postnatal days 4-7 and 10-13 for 4?h/day. Behavioral outcomes measured were locomotor activity, novel object recognition (short-term memory), elevated plus maze (anxiety-like behavior), fixed interval (FI) schedule of food reward (learning, timing) and differential reinforcement of low rate (DRL) schedule of food reward (impulsivity, inability to inhibit responding). Neuropathology was assessed by measures of inflammation (glial fibrillary-acidic protein), myelin basic protein expression in the corpus callosum, and lateral ventricle area. RESULTS:Twenty-four hours following the final exposure day, no significant differences in anogenital distance, body weight or central nervous system pathological markers were observed in offspring of either sex. Nor were significant changes observed in novel object recognition, elevated plus maze performance, FI, or DRL schedule-controlled behavior in either females or males. CONCLUSION:The limited effect of neonatal exposure to ultrafine elemental carbon suggests this component of air pollution is not a substantial contributor to the behavioral alterations and neuropathology previously observed in response to ambient pollution particulate exposures. Rather, other more reactive constituent species, organic and/or inorganic, gas-phase components, or combinations of constituents may be involved. Defining these neurotoxic components is critical to the formulation of better animal models, more focused mechanistic assessments, and potential regulatory policies for air pollution.

Project description:BackgroundEpidemiologic and animal studies have shown that particulate air pollution is associated with increased risk of lung and cardiovascular diseases. Although the exact mechanisms by which particles induce cardiovascular diseases are not known, studies suggest involvement of systemic acute phase responses, including C-reactive protein (CRP) and serum amyloid A (SAA) in humans. In this study we test the hypothesis that diesel exhaust particles (DEP) - or carbon black (CB)-induced lung inflammation initiates an acute phase response in the liver.ResultsMice were exposed to filtered air, 20 mg/m3 DEP or CB by inhalation for 90 minutes/day for four consecutive days; we have previously shown that these mice exhibit pulmonary inflammation (Saber AT, Bornholdt J, Dybdahl M, Sharma AK, Loft S, Vogel U, Wallin H. Tumor necrosis factor is not required for particle-induced genotoxicity and pulmonary inflammation., Arch. Toxicol. 79 (2005) 177-182). As a positive control for the induction of an acute phase response, mice were exposed to 12.5 mg/kg of lipopolysaccharide (LPS) intraperitoneally. Quantitative real time RT-PCR was used to examine the hepatic mRNA expression of acute phase proteins, serum amyloid P (Sap) (the murine homologue of Crp) and Saa1 and Saa3. While significant increases in the hepatic expression of Sap, Saa1 and Saa3 were observed in response to LPS, their levels did not change in response to DEP or CB. In a comprehensive search for markers of an acute phase response, we analyzed liver tissue from these mice using high density DNA microarrays. Globally, 28 genes were found to be significantly differentially expressed in response to DEP or CB. The mRNA expression of three of the genes (serine (or cysteine) proteinase inhibitor, clade A, member 3C, apolipoprotein E and transmembrane emp24 domain containing 3) responded to both exposures. However, these changes were very subtle and were not confirmed by real time RT-PCR.ConclusionOur findings collectively suggest that Sap, Saa1 and Saa3 are not induced in livers of mice exposed to DEP or CB. Despite pulmonary inflammation in these mice, global transcriptional profiling of liver did not reveal any hepatic response following exposure by inhalation.

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Dataset Information

Limited developmental neurotoxicity from neonatal inhalation exposure to diesel exhaust particles in C57BL/6 mice.

Background

Results

Conclusion

Publications

Limited developmental neurotoxicity from neonatal inhalation exposure to diesel exhaust particles in C57BL/6 mice.

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