Maternal immune activation in mice disrupts proteostasis in the fetal brain.
Nat Neurosci
; 24(2): 204-213, 2021 02.
Article
em En
| MEDLINE
| ID: mdl-33361822
ABSTRACT
Maternal infection and inflammation during pregnancy are associated with neurodevelopmental disorders in offspring, but little is understood about the molecular mechanisms underlying this epidemiologic phenomenon. Here, we leveraged single-cell RNA sequencing to profile transcriptional changes in the mouse fetal brain in response to maternal immune activation (MIA) and identified perturbations in cellular pathways associated with mRNA translation, ribosome biogenesis and stress signaling. We found that MIA activates the integrated stress response (ISR) in male, but not female, MIA offspring in an interleukin-17a-dependent manner, which reduced global mRNA translation and altered nascent proteome synthesis. Moreover, blockade of ISR activation prevented the behavioral abnormalities as well as increased cortical neural activity in MIA male offspring. Our data suggest that sex-specific activation of the ISR leads to maternal inflammation-associated neurodevelopmental disorders.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Encéfalo
/
Feto
/
Proteostase
/
Imunidade Inata
Tipo de estudo:
Prognostic_studies
Limite:
Animals
/
Pregnancy
Idioma:
En
Revista:
Nat Neurosci
Ano de publicação:
2021
Tipo de documento:
Article