Maternal immune activation leads to defective brain-blood vessels and intracerebral hemorrhages in male offspring.

Autor: Rasile M; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Lauranzano E; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Faggiani E; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Ravanelli MM; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Colombo FS; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Mirabella F; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Corradini I; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.; Institute of Neuroscience (IN-CNR), National Research Council of Italy, Milan, Italy., Malosio ML; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.; Institute of Neuroscience (IN-CNR), National Research Council of Italy, Milan, Italy., Borreca A; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy.; Institute of Neuroscience (IN-CNR), National Research Council of Italy, Milan, Italy., Focchi E; Institute of Neuroscience (IN-CNR), National Research Council of Italy, Milan, Italy., Pozzi D; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Giorgino T; Institute of Biophysics (IBF-CNR), National Research Council of Italy, Milan, Italy., Barajon I; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; IRCCS Humanitas Clinical and Research Center, Rozzano, Italy., Matteoli M; Department of Biomedical Sciences, Humanitas University, Pieve Emanuele, Italy.; Institute of Neuroscience (IN-CNR), National Research Council of Italy, Milan, Italy.
Jazyk: angličtina
Zdroj: The EMBO journal [EMBO J] 2022 Dec 01; Vol. 41 (23), pp. e111192. Date of Electronic Publication: 2022 Oct 31.
DOI: 10.15252/embj.2022111192
Abstrakt: 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.
(© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.)
Databáze: MEDLINE
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