Effects of maternal exposure to ultrafine carbon black on brain perivascular macrophages and surrounding astrocytes in offspring mice.
Perivascular macrophages (PVMs) constitute a subpopulation of resident macrophages in the central nervous system (CNS). They are located at the blood-brain barrier and can contribute to maintenance of brain functions in both health and disease conditions. PVMs have been shown to respond to particle substances administered during the prenatal period, which may alter their phenotype over a long period. We aimed to investigate the effects of maternal exposure to ultrafine carbon black (UfCB) on PVMs and astrocytes close to the blood vessels in offspring mice. Pregnant mice were exposed to UfCB suspension by intranasal instillation on gestational days 5 and 9. Brains were collected from their offspring at 6 and 12 weeks after birth. PVM and astrocyte phenotypes were examined by Periodic Acid Schiff (PAS) staining, transmission electron microscopy and PAS-glial fibrillary acidic protein (GFAP) double staining. PVM granules were found to be enlarged and the number of PAS-positive PVMs was decreased in UfCB-exposed offspring. These results suggested that in offspring, "normal" PVMs decreased in a wide area of the CNS through maternal UfCB exposure. The increase in astrocytic GFAP expression level was closely related to the enlargement of granules in the attached PVMs in offspring. Honeycomb-like structures in some PVM granules and swelling of astrocytic end-foot were observed under electron microscopy in the UfCB group. The phenotypic changes in PVMs and astrocytes indicate that maternal UfCB exposure may result in changes to brain blood vessels and be associated with increased risk of dysfunction and disorder in the offspring brain.
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan; Department of Pathology, Tochigi Institute of Clinical Pathology, Nogi, Tochigi, Japan.
Atsuto
A
Onoda
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan; The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Masakazu
M
Umezawa
Department of Hygienic Chemistry, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Noda, Chiba, Japan; The Center for Environmental Health Science for the Next Generation, Research Institute for Science and Technology, Tokyo University of Science, Noda, Chiba, Japan.
Ken
K
Takeda
Department of Pathology, Tochigi Institute of Clinical Pathology, Nogi, Tochigi, Japan.
Tomomi
T
Ihara
Department of Pathology, Tochigi Institute of Clinical Pathology, Nogi, Tochigi, Japan.
Masao
M
Sugamata
D000281:Administration, Intranasal; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology / Q000648:ultrastructure*; D005260:Female; D015870:Gene Expression; D005904:Glial Fibrillary Acidic Protein; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D018811:Maternal Exposure; D051379:Mice; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D012744:Sex Ratio; D053260:Soot / Q000008:administration & dosage*
D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D053260:Soot; C528900:glial fibrillary astrocytic protein, mouse