Maternal administration of nanomaterials elicits hemoglobin upregulation in the neonatal brain of non-human primates

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  • Mitsunaga Fusako
    Biomedical Institute, NPO Primate Agora The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science Primate Research Institute, Kyoto University
  • Umezawa Masakazu
    The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Takeda Ken
    The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science
  • Nakamura Shin
    Biomedical Institute, NPO Primate Agora The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Organization for Research Advancement, Tokyo University of Science Primate Research Institute, Kyoto University Intelligence and Technology Lab Inc

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Abstract

To investigate the influence of nanomaterial exposure during fetal development, diesel exhaust particles (DEPs), carbon black (CB), or titanium dioxide (TiO2) was injected intradermally to pregnant rhesus macaques. The hippocampus and cerebellum of newborn infants were then examined. DNA microarray and quantitative real-time RT-PCR, western blot, and immunohistochemical analyses were used to measure the expression of the hemoglobin genes, HBA, HBB, and HBG. Of the nanomaterials tested, DEP elicited the greatest increase in mRNA and protein levels of hemoglobin genes in the brain tissues. Strong signal of HbA protein was detected in the pyramidal cell layer, the polymorphic cell layer and in the alveus of the hippocampi of the DEP-treated animals. The altered gene expression was likely due to responses to oxidative or nitrosative stress and/or hypoxia in the fetal/neonatal brain. Since excessive hemoglobin is reportedly neurotoxic, the vulnerability of developing brains by long-term upregulation of hemoglobin should be considered. Maternal exposure to nanomaterials may increase the risk of brain dysfunction in offspring.

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