Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders
Abstract Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the rol...
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Nature Portfolio
2025-01-01
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| Series: | Communications Biology |
| Online Access: | https://doi.org/10.1038/s42003-025-07511-3 |
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| author | Kazuya Fuma Yukako Iitani Kenji Imai Takafumi Ushida Sho Tano Kosuke Yoshida Akira Yokoi Rika Miki Hiroyuki Kidokoro Yoshiaki Sato Yuichiro Hara Tomoo Ogi Kohei Nomaki Makoto Tsuda Okiru Komine Koji Yamanaka Hiroaki Kajiyama Tomomi Kotani |
| author_facet | Kazuya Fuma Yukako Iitani Kenji Imai Takafumi Ushida Sho Tano Kosuke Yoshida Akira Yokoi Rika Miki Hiroyuki Kidokoro Yoshiaki Sato Yuichiro Hara Tomoo Ogi Kohei Nomaki Makoto Tsuda Okiru Komine Koji Yamanaka Hiroaki Kajiyama Tomomi Kotani |
| author_sort | Kazuya Fuma |
| collection | DOAJ |
| description | Abstract Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c+ microglia, key contributors to myelination through IGF-1 production, in this pathology. In the mouse model, the CD11c+ microglial population was significantly lower in the MIA group than in the control group on postnatal day 3 (PN3d). Furthermore, myelination-related protein levels significantly decreased in the MIA group at PN8d. In humans, preterm infants with HCA exhibited higher IL-6 and IL-17A cord-serum levels and lower IGF-1 levels than those without HCA, followed by a higher incidence of delayed myelination on magnetic resonance imaging at the term-equivalent age. In silico analysis revealed that the transient induction of CD11c+ microglia during early development occurred similarly in mice and humans. Notably, a lack of high CD11c+ microglial population has been observed in children with neurodevelopmental disorders. This study reports impaired induction of CD11c+ microglia during postnatal development in a mouse model of MIA associated with delayed myelination. Our findings may inform strategies for improving outcomes in infants with HCA. |
| format | Article |
| id | doaj-art-73f8be4c905f42a786dc8d0b075025db |
| institution | Kabale University |
| issn | 2399-3642 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Communications Biology |
| spelling | doaj-art-73f8be4c905f42a786dc8d0b075025db2025-01-19T12:35:23ZengNature PortfolioCommunications Biology2399-36422025-01-018111310.1038/s42003-025-07511-3Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disordersKazuya Fuma0Yukako Iitani1Kenji Imai2Takafumi Ushida3Sho Tano4Kosuke Yoshida5Akira Yokoi6Rika Miki7Hiroyuki Kidokoro8Yoshiaki Sato9Yuichiro Hara10Tomoo Ogi11Kohei Nomaki12Makoto Tsuda13Okiru Komine14Koji Yamanaka15Hiroaki Kajiyama16Tomomi Kotani17Department of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineLaboratory of Bell Research Center‑Department of Obstetrics and Gynecology Collaborative Research, Nagoya University Graduate School of MedicineDepartment of Pediatrics, Nagoya University Graduate School of MedicineDivision of Neonatology, Center for Maternal-Neonatal Care, Nagoya University HospitalDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya UniversityDepartment of Genetics, Research Institute of Environmental Medicine, Nagoya UniversityDepartment of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Molecular and System Pharmacology, Graduate School of Pharmaceutical Sciences, Kyushu UniversityDepartment of Neuroscience and Pathobiology, Nagoya University Graduate School of MedicineInstitute for Glyco-core Research (iGCORE), Nagoya UniversityDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of MedicineAbstract Histological chorioamnionitis (HCA) is a form of maternal immune activation (MIA) linked to an increased risk of neurodevelopmental disorders in offspring. Our previous study identified neurodevelopmental impairments in an MIA mouse model mimicking HCA. Thus, this study investigated the role of CD11c+ microglia, key contributors to myelination through IGF-1 production, in this pathology. In the mouse model, the CD11c+ microglial population was significantly lower in the MIA group than in the control group on postnatal day 3 (PN3d). Furthermore, myelination-related protein levels significantly decreased in the MIA group at PN8d. In humans, preterm infants with HCA exhibited higher IL-6 and IL-17A cord-serum levels and lower IGF-1 levels than those without HCA, followed by a higher incidence of delayed myelination on magnetic resonance imaging at the term-equivalent age. In silico analysis revealed that the transient induction of CD11c+ microglia during early development occurred similarly in mice and humans. Notably, a lack of high CD11c+ microglial population has been observed in children with neurodevelopmental disorders. This study reports impaired induction of CD11c+ microglia during postnatal development in a mouse model of MIA associated with delayed myelination. Our findings may inform strategies for improving outcomes in infants with HCA.https://doi.org/10.1038/s42003-025-07511-3 |
| spellingShingle | Kazuya Fuma Yukako Iitani Kenji Imai Takafumi Ushida Sho Tano Kosuke Yoshida Akira Yokoi Rika Miki Hiroyuki Kidokoro Yoshiaki Sato Yuichiro Hara Tomoo Ogi Kohei Nomaki Makoto Tsuda Okiru Komine Koji Yamanaka Hiroaki Kajiyama Tomomi Kotani Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders Communications Biology |
| title | Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders |
| title_full | Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders |
| title_fullStr | Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders |
| title_full_unstemmed | Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders |
| title_short | Prenatal inflammation impairs early CD11c-positive microglia induction and delays myelination in neurodevelopmental disorders |
| title_sort | prenatal inflammation impairs early cd11c positive microglia induction and delays myelination in neurodevelopmental disorders |
| url | https://doi.org/10.1038/s42003-025-07511-3 |
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