Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring

Masakazu Umezawa, Atsuto Onoda, Irina Korshunova, Alexander C. O. Jensen, Ismo K. Koponen, Keld A. Jensen, Konstantin Khodosevich, Ulla Birgitte Vogel, Karin S. Hougaard*

*Corresponding author for this work

    Research output: Contribution to journalJournal articleResearchpeer-review

    106 Downloads (Pure)

    Abstract

    Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90).Methods: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test.Results: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 2829 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated.Conclusion: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.
    Original languageEnglish
    JournalParticle and Fibre Toxicology
    Volume15
    Issue number36
    Number of pages18
    ISSN1743-8977
    DOIs
    Publication statusPublished - 2018

    Keywords

    • Carbon black
    • Maternal exposure
    • Prenatal exposure
    • Pregnancy
    • Brain
    • Nanoparticle
    • Behaviour
    • Astrocyte
    • Neurodevelopment
    • Developmental neurotoxicity

    Cite this

    Umezawa, M., Onoda, A., Korshunova, I., Jensen, A. C. O., Koponen, I. K., Jensen, K. A., ... Hougaard, K. S. (2018). Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring. Particle and Fibre Toxicology, 15(36). https://doi.org/10.1186/s12989-018-0272-2
    Umezawa, Masakazu ; Onoda, Atsuto ; Korshunova, Irina ; Jensen, Alexander C. O. ; Koponen, Ismo K. ; Jensen, Keld A. ; Khodosevich, Konstantin ; Vogel, Ulla Birgitte ; Hougaard, Karin S. / Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring. In: Particle and Fibre Toxicology. 2018 ; Vol. 15, No. 36.
    @article{98730578f5ad4ed29d19eb60b62afbdd,
    title = "Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring",
    abstract = "Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90).Methods: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test.Results: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 2829 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated.Conclusion: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.",
    keywords = "Carbon black, Maternal exposure, Prenatal exposure, Pregnancy, Brain, Nanoparticle, Behaviour, Astrocyte, Neurodevelopment, Developmental neurotoxicity",
    author = "Masakazu Umezawa and Atsuto Onoda and Irina Korshunova and Jensen, {Alexander C. O.} and Koponen, {Ismo K.} and Jensen, {Keld A.} and Konstantin Khodosevich and Vogel, {Ulla Birgitte} and Hougaard, {Karin S.}",
    year = "2018",
    doi = "10.1186/s12989-018-0272-2",
    language = "English",
    volume = "15",
    journal = "Particle and Fibre Toxicology",
    issn = "1743-8977",
    publisher = "BioMed Central",
    number = "36",

    }

    Umezawa, M, Onoda, A, Korshunova, I, Jensen, ACO, Koponen, IK, Jensen, KA, Khodosevich, K, Vogel, UB & Hougaard, KS 2018, 'Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring', Particle and Fibre Toxicology, vol. 15, no. 36. https://doi.org/10.1186/s12989-018-0272-2

    Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring. / Umezawa, Masakazu; Onoda, Atsuto; Korshunova, Irina; Jensen, Alexander C. O.; Koponen, Ismo K.; Jensen, Keld A.; Khodosevich, Konstantin; Vogel, Ulla Birgitte; Hougaard, Karin S.

    In: Particle and Fibre Toxicology, Vol. 15, No. 36, 2018.

    Research output: Contribution to journalJournal articleResearchpeer-review

    TY - JOUR

    T1 - Maternal inhalation of carbon black nanoparticles induces neurodevelopmental changes in mouse offspring

    AU - Umezawa, Masakazu

    AU - Onoda, Atsuto

    AU - Korshunova, Irina

    AU - Jensen, Alexander C. O.

    AU - Koponen, Ismo K.

    AU - Jensen, Keld A.

    AU - Khodosevich, Konstantin

    AU - Vogel, Ulla Birgitte

    AU - Hougaard, Karin S.

    PY - 2018

    Y1 - 2018

    N2 - Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90).Methods: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test.Results: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 2829 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated.Conclusion: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.

    AB - Background: Engineered nanoparticles are smaller than 100 nm and designed to improve or creating even new physico-chemical properties. Consequently, toxicological properties of materials may change as size reaches the nm size-range. We examined outcomes related to the central nervous system in the offspring following maternal inhalation exposure to nanosized carbon black particles (Printex 90).Methods: Time-mated mice (NMRI) were exposed by inhalation, for 45 min/day to 0, 4.6 or 37 mg/m3 aerosolized carbon black on gestation days 4-18, i.e. for a total of 15 days. Outcomes included maternal lung inflammation (differential cell count in bronchoalveolar lavage fluid and Saa3 mRNA expression in lung tissue), offspring neurohistopathology and behaviour in the open field test.Results: Carbon black exposure did not cause lung inflammation in the exposed females, measured 11 or 2829 days post-exposure. Glial fibrillary acidic protein (GFAP) expression levels were dose-dependently increased in astrocytes around blood vessels in the cerebral cortex and hippocampus in six weeks old offspring, indicative of reactive astrogliosis. Also enlarged lysosomal granules were observed in brain perivascular macrophages (PVMs) in the prenatally exposed offspring. The number of parvalbumin-positive interneurons and the expression levels of parvalbumin were decreased in the motor and prefrontal cortices at weaning and 120 days of age in the prenatally exposed offspring. In the open field test, behaviour was dose-dependently altered following maternal exposure to Printex 90, at 90 days of age. Prenatally exposed female offspring moved a longer total distance, and especially males spent significantly longer time in the central zone of the maze. In the offspring, the described effects were long-lasting as they were present at all time points investigated.Conclusion: The present study reports for the first time that maternal inhalation exposure to Printex 90 carbon black induced dose-dependent denaturation of PVM and reactive astrocytes, similarly to the findings observed following maternal exposure to Printex 90 by airway instillation. Of note, some of the observed effects have striking similarities with those observed in mouse models of neurodevelopmental disorders.

    KW - Carbon black

    KW - Maternal exposure

    KW - Prenatal exposure

    KW - Pregnancy

    KW - Brain

    KW - Nanoparticle

    KW - Behaviour

    KW - Astrocyte

    KW - Neurodevelopment

    KW - Developmental neurotoxicity

    U2 - 10.1186/s12989-018-0272-2

    DO - 10.1186/s12989-018-0272-2

    M3 - Journal article

    VL - 15

    JO - Particle and Fibre Toxicology

    JF - Particle and Fibre Toxicology

    SN - 1743-8977

    IS - 36

    ER -