Preeclampsia promotes autism in offspring via maternal inflammation and fetal NFκB signaling.
Life Sci Alliance
; 6(8)2023 08.
Article
em En
| MEDLINE
| ID: mdl-37290815
ABSTRACT
Preeclampsia (PE) is a risk factor for autism spectrum disorder (ASD) in offspring. However, the exact mechanisms underlying the impact of PE on progeny ASD are not fully understood, which hinders the development of effective therapeutic approaches. This study shows the offspring born to a PE mouse model treated by Nω-nitro-L-arginine methyl ester (L-NAME) exhibit ASD-like phenotypes, including neurodevelopment deficiency and behavioral abnormalities. Transcriptomic analysis of the embryonic cortex and adult offspring hippocampus suggested the expression of ASD-related genes was dramatically changed. Furthermore, the level of inflammatory cytokines TNFα in maternal serum and nuclear factor kappa B (NFκB) signaling in the fetal cortex were elevated. Importantly, TNFα neutralization during pregnancy enabled to ameliorate ASD-like phenotypes and restore the NFκB activation level in the offspring exposed to PE. Furthermore, TNFα/NFκB signaling axis, but not L-NAME, caused deficits in neuroprogenitor cell proliferation and synaptic development. These experiments demonstrate that offspring exposed to PE phenocopies ASD signatures reported in humans and indicate therapeutic targeting of TNFα decreases the likelihood of bearing children with ASD phenotypes from PE mothers.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Pré-Eclâmpsia
/
Efeitos Tardios da Exposição Pré-Natal
/
Transtorno Autístico
/
Transtorno do Espectro Autista
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Animals
/
Child
/
Female
/
Humans
/
Pregnancy
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article