Maternal immune activation leads to defective brain-blood vessels and intracerebral hemorrhages in male offspring.
CD146
MIA
NVU
intracerebral hemorrhages
sex dimorphism
Journal
The EMBO journal
ISSN: 1460-2075
Titre abrégé: EMBO J
Pays: England
ID NLM: 8208664
Informations de publication
Date de publication:
01 12 2022
01 12 2022
Historique:
revised:
21
09
2022
received:
16
03
2022
accepted:
27
09
2022
pubmed:
1
11
2022
medline:
3
12
2022
entrez:
31
10
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36314682
doi: 10.15252/embj.2022111192
pmc: PMC9713716
doi:
Substances chimiques
Poly I-C
O84C90HH2L
Transforming Growth Factor beta1
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e111192Commentaires et corrections
Type : ErratumIn
Informations de copyright
© 2022 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
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