Maternal immune activation leads to defective brain-blood vessels and intracerebral hemorrhages in male offspring
| Autor: | Marco Rasile, Eliana Lauranzano, Elisa Faggiani, Margherita M Ravanelli, Federico S Colombo, Filippo Mirabella, Irene Corradini, Maria L Malosio, Antonella Borreca, Elisa Focchi, Davide Pozzi, Toni Giorgino, Isabella Barajon, Michela Matteoli |
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| Rok vydání: | 2022 |
| Předmět: |
Male
General Immunology and Microbiology Behavior Animal General Neuroscience Brain Endothelial Cells General Biochemistry Genetics and Molecular Biology Transforming Growth Factor beta1 Mice Disease Models Animal Poly I-C Pregnancy Prenatal Exposure Delayed Effects Animals Female Molecular Biology Cerebral Hemorrhage |
| Zdroj: | The EMBO journal. 41(23) |
| ISSN: | 1460-2075 |
| Popis: | Intracerebral hemorrhages are recognized risk factors for neurodevelopmental disorders and represent early biomarkers for cognitive dysfunction and mental disability, but the pathways leading to their occurrence are not well defined. We report that a single intrauterine exposure of the immunostimulant Poly I:C to pregnant mice at gestational day 9, which models a prenatal viral infection and the consequent maternal immune activation, induces the defective formation of brain vessels and causes intracerebral hemorrhagic events, specifically in male offspring. We demonstrate that maternal immune activation promotes the production of the TGF-β1 active form and the consequent enhancement of pSMAD1-5 in males' brain endothelial cells. TGF-β1, in combination with IL-1β, reduces the endothelial expression of CD146 and claudin-5, alters the endothelium-pericyte interplay resulting in low pericyte coverage, and increases hemorrhagic events in the adult offspring. By showing that exposure to Poly I:C at the beginning of fetal cerebral angiogenesis results in sex-specific alterations of brain vessels, we provide a mechanistic framework for the association between intragravidic infections and anomalies of the neural vasculature, which may contribute to neuropsychiatric disorders. |
| Databáze: | OpenAIRE |
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