The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice
Abstract Background Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain...
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| Format: | Article |
| Language: | English |
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BMC
2022-08-01
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| Series: | Particle and Fibre Toxicology |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12989-022-00496-5 |
| _version_ | 1828182850855239680 |
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| author | Marissa Sobolewski Katherine Conrad Elena Marvin Matthew Eckard Calla M. Goeke Alyssa K. Merrill Kevin Welle Brian P. Jackson Robert Gelein David Chalupa Günter Oberdörster Deborah A. Cory-Slechta |
| author_facet | Marissa Sobolewski Katherine Conrad Elena Marvin Matthew Eckard Calla M. Goeke Alyssa K. Merrill Kevin Welle Brian P. Jackson Robert Gelein David Chalupa Günter Oberdörster Deborah A. Cory-Slechta |
| author_sort | Marissa Sobolewski |
| collection | DOAJ |
| description | Abstract Background Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain metal dyshomeostasis, including significant increases in brain Fe. Since Fe is redox active and neurotoxic to brain in excess, this study examined the extent to which postnatal Fe inhalation exposure, might contribute to the observed neurotoxicity of UFPs. Mice were exposed to 1 µg/m3 Fe oxide nanoparticles alone, or in conjunction with sulfur dioxide (Fe (1 µg/m3) + SO2 (SO2 at 1.31 mg/m3, 500 ppb) from postnatal days 4–7 and 10–13 for 4 h/day. Results Overarching results included the observations that Fe + SO2 produced greater neurotoxicity than did Fe alone, that females appeared to show greater vulnerability to these exposures than did males, and that profiles of effects differed by sex. Consistent with metal dyshomeostasis, both Fe only and Fe + SO2 exposures altered correlations of Fe and of sulfur (S) with other metals in a sex and tissue-specific manner. Specifically, altered metal levels in lung, but particularly in frontal cortex were found, with reductions produced by Fe in females, but increases produced by Fe + SO2 in males. At PND14, marked changes in brain frontal cortex and striatal neurotransmitter systems were observed, particularly in response to combined Fe + SO2 as compared to Fe only, in glutamatergic and dopaminergic functions that were of opposite directions by sex. Changes in markers of trans-sulfuration in frontal cortex likewise differed in females as compared to males. Residual neurotransmitter changes were limited at PND60. Increases in serum glutathione and Il-1a were female-specific effects of combined Fe + SO2. Conclusions Collectively, these findings suggest a role for the Fe contamination in air pollution in the observed neurotoxicity of ambient UFPs and that such involvement may be different by chemical mixture. Translation of such results to humans requires verification, and, if found, would suggest a need for regulation of Fe in air for public health protection. |
| first_indexed | 2024-04-12T06:24:04Z |
| format | Article |
| id | doaj.art-d104b2fcdd72401393f5be333fec41c8 |
| institution | Directory Open Access Journal |
| issn | 1743-8977 |
| language | English |
| last_indexed | 2024-04-12T06:24:04Z |
| publishDate | 2022-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Particle and Fibre Toxicology |
| spelling | doaj.art-d104b2fcdd72401393f5be333fec41c82022-12-22T03:44:13ZengBMCParticle and Fibre Toxicology1743-89772022-08-0119111910.1186/s12989-022-00496-5The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in miceMarissa Sobolewski0Katherine Conrad1Elena Marvin2Matthew Eckard3Calla M. Goeke4Alyssa K. Merrill5Kevin Welle6Brian P. Jackson7Robert Gelein8David Chalupa9Günter Oberdörster10Deborah A. Cory-Slechta11Department of Environmental Medicine, University of Rochester Medical CenterDepartment of Environmental Medicine, University of Rochester Medical CenterDepartment of Environmental Medicine, University of Rochester Medical CenterDepartment of Psychology, Radford UniversityDepartment of Environmental Medicine, University of Rochester Medical CenterDepartment of Environmental Medicine, University of Rochester Medical CenterProteomics Core, University of Rochester Medical CenterDepartment of Earth Sciences, Dartmouth CollegeDepartment of Environmental Medicine, University of Rochester Medical CenterDepartment of Environmental Medicine, University of Rochester Medical CenterDepartment of Environmental Medicine, University of Rochester Medical CenterDepartment of Environmental Medicine, University of Rochester Medical CenterAbstract Background Air pollution has been associated with neurodevelopmental disorders in epidemiological studies. In our studies in mice, developmental exposures to ambient ultrafine particulate (UFP) matter either postnatally or gestationally results in neurotoxic consequences that include brain metal dyshomeostasis, including significant increases in brain Fe. Since Fe is redox active and neurotoxic to brain in excess, this study examined the extent to which postnatal Fe inhalation exposure, might contribute to the observed neurotoxicity of UFPs. Mice were exposed to 1 µg/m3 Fe oxide nanoparticles alone, or in conjunction with sulfur dioxide (Fe (1 µg/m3) + SO2 (SO2 at 1.31 mg/m3, 500 ppb) from postnatal days 4–7 and 10–13 for 4 h/day. Results Overarching results included the observations that Fe + SO2 produced greater neurotoxicity than did Fe alone, that females appeared to show greater vulnerability to these exposures than did males, and that profiles of effects differed by sex. Consistent with metal dyshomeostasis, both Fe only and Fe + SO2 exposures altered correlations of Fe and of sulfur (S) with other metals in a sex and tissue-specific manner. Specifically, altered metal levels in lung, but particularly in frontal cortex were found, with reductions produced by Fe in females, but increases produced by Fe + SO2 in males. At PND14, marked changes in brain frontal cortex and striatal neurotransmitter systems were observed, particularly in response to combined Fe + SO2 as compared to Fe only, in glutamatergic and dopaminergic functions that were of opposite directions by sex. Changes in markers of trans-sulfuration in frontal cortex likewise differed in females as compared to males. Residual neurotransmitter changes were limited at PND60. Increases in serum glutathione and Il-1a were female-specific effects of combined Fe + SO2. Conclusions Collectively, these findings suggest a role for the Fe contamination in air pollution in the observed neurotoxicity of ambient UFPs and that such involvement may be different by chemical mixture. Translation of such results to humans requires verification, and, if found, would suggest a need for regulation of Fe in air for public health protection.https://doi.org/10.1186/s12989-022-00496-5Ultrafine particulate matterIronSulfur dioxideNeurodevelopmental disordersBrainMetal dyshomeostasis |
| spellingShingle | Marissa Sobolewski Katherine Conrad Elena Marvin Matthew Eckard Calla M. Goeke Alyssa K. Merrill Kevin Welle Brian P. Jackson Robert Gelein David Chalupa Günter Oberdörster Deborah A. Cory-Slechta The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice Particle and Fibre Toxicology Ultrafine particulate matter Iron Sulfur dioxide Neurodevelopmental disorders Brain Metal dyshomeostasis |
| title | The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice |
| title_full | The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice |
| title_fullStr | The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice |
| title_full_unstemmed | The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice |
| title_short | The potential involvement of inhaled iron (Fe) in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice |
| title_sort | potential involvement of inhaled iron fe in the neurotoxic effects of ultrafine particulate matter air pollution exposure on brain development in mice |
| topic | Ultrafine particulate matter Iron Sulfur dioxide Neurodevelopmental disorders Brain Metal dyshomeostasis |
| url | https://doi.org/10.1186/s12989-022-00496-5 |
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