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Cited by 77Immunotoxicology and immune responsesNeuroinflammation and Neurodegeneration MechanismsAir Quality and Health Impacts

Dose-dependent induction of astrocyte activation and reactive astrogliosis in mouse brain following maternal exposure to carbon black nanoparticle

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Onoda, Atsuto, Takeda, Ken, Umezawa, Masakazu·2017·Particle and Fibre Toxicology
DOI 10.1186/s12989-017-0184-6PMC PMC5289048
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Abstract

BACKGROUND: Recent studies indicate that maternal exposure to ambient ultrafine particles and nanoparticles has adverse effects of on the central nervous system. Quantitative dose-response data is required to better understand the developmental neurotoxicity of nanoparticles. The present study investigated dose-dependent effects of maternal exposure to carbon black nanoparticle (CB-NP) on astrocyte in the brains of mouse offspring. METHODS: A CB-NP suspension (2.9, 15, or 73 μg/kg) was intranasally administered to pregnant ICR mice on gestational days 5 and 9. Cerebral cortex samples were collected from 6-week-old offspring and examined by Western blotting, immunostaining, microarray analysis, and quantitative reverse transcriptase-polymerase chain reaction. Placentae were collected from pregnant dams on gestational day 13 and examined by microarray analysis. RESULTS: Maternal exposure to CB-NP induced a dose-dependent increase in glial fibrillary acidic protein (GFAP) expression in the cerebral cortex; this increase was particularly observed in astrocytic end-feet attached to denatured perivascular macrophages. Moreover, maternal CB-NP exposure dose-dependently increased aquaporin-4 expression in the brain parenchyma region around blood vessels. The changes in the expression profiles of GFAP and Aqp4 in offspring after maternal CB-NP exposure were similar to those observed in mice of a more advanced age. The expression levels of mRNAs associated with angiogenesis, cell migration, proliferation, chemotaxis, and growth factor production were also altered in the cerebral cortex of offspring after maternal CB-NP exposure. Differentially expressed genes in placental tissues after CB-NP exposure did not populate any specific gene ontology category. CONCLUSIONS: Maternal CB-NP exposure induced long-term activation of astrocytes resulting in reactive astrogliosis in the brains of young mice. Our observations suggest a potentially increased risk of the onset of age-related neurodegenerative diseases by maternal NP exposure. In this study, we report for the first time a quantitative dose-response relationship between maternal NP exposure and phenotypic changes in the central nervous system of the offspring. Moreover, our findings indicate that cortical GFAP and Aqp4 are useful biomarkers that can be employed in further studies aiming to elucidate the underlying mechanism of nanoparticle-mediated developmental neurotoxicity.

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  • Increased expression of glial fibrillary acidic protein has consistently been correlated with developmental PM2.5 and PM0.1 exposure.

    “Increased expression of the glial fibrillary acidic protein (GFAP), a marker of activated astrocytes, has consistently been correlated with developmental PM2.5 and PM0.1 exposure [113, 114].”

    From Air pollution and children’s health—a review of adverse effects associated with prenatal exposure from fine to ultrafine particulate matter (2021) · cites this paper as [113]

    The Results (GFAP expression levels in the cerebral cortex) report significantly increased GFAP in offspring after middle- and high-dose maternal carbon black nanoparticle exposure. The study supports an association for this nanoparticle exposure, but does not establish that the finding is consistent across developmental PM2.5 and PM0.1 exposures. (LLM, conf=0.84)

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Authors
Onoda, A., Takeda, K., & Umezawa, M.
Affiliations
Tokyo University of Science (JP)
Corresponding author
Onoda, Atsuto
ORCID
Venue
Particle and Fibre Toxicology
Publisher
Springer Science and Business Media LLC
Published
2017-02-02
Volume
14
Issue
1
Pages
4-4
ISSN
1743-8977 (ISSN-L)
DOI
10.1186/s12989-017-0184-6
PMC
PMC5289048
OpenAlex
W2585902254
Cited by
77
References
5
Citations by year
2026: 3 · 2025: 5 · 2024: 5 · 2023: 8 · 2022: 9 · 2021: 9 · 2020: 11 · 2019: 11 · 2018: 9 · 2017: 6 · 2016: 1
FWCI
4.58
Type
journal article
Language
en
Open access
Licence
Locations
  • Particle and Fibre Toxicology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • Ministry of Education, Culture, Sports, Science, and Technology (S1101015)
  • Japan Society for the Promotion of Science (15J05718)
Topics
  • Life Sciences › Immunology and Microbiology › Immunology › Immunotoxicology and immune responses
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Air Quality and Health Impacts
Keywords
carbon black nanoparticles, developmental neurotoxicity, reactive astrogliosis, astrocyte activation, glial fibrillary acidic protein, aquaporin-4, cerebral cortex, placenta, dose-response relationship, biomarkers, neurodegenerative disease risk, intranasal exposure
MeSH terms
Animals, Astrocytes, Body Weight, Cerebral Cortex, Female, Glial Fibrillary Acidic Protein, Litter Size, Male, Mice, Inbred ICR, Pregnancy, Maternal Exposure, Gene Expression Profiling, Mice, Aquaporin 4, Soot, Nanoparticles, Real-Time Polymerase Chain Reaction

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