Mid-pregnancy maternal immune activation increases Pax6-positive and Tbr2-positive neural progenitor cells and causes integrated stress response in the fetal brain in a mouse model of maternal viral infection.
IBRO Neurosci Rep
; 11: 73-80, 2021 Dec.
Article
en En
| MEDLINE
| ID: mdl-34409402
ABSTRACT
Maternal immune activation (MIA) in midpregnancy is a risk factor for neurodevelopmental disorders. Improper brain development may cause malformations of the brain; maldevelopment induced by MIA may lead to a pathology-related phenotype. In this study, a single intraperitoneal injection of 20 mg/kg polyriboinosinic-polyribocytidylic acid [poly(IC)] was administered to C57BL/6J mice on embryonic day (E) 12.5 to mimic maternal viral infection. Histopathological analysis of neurogenesis was performed using markers for Pax6, Tbr2, and Tbr1. In these fetuses, significant increases were observed in the proportion of Pax6-positive neural progenitor cells and Pax6/Tbr2 double-positive cells 24 h after poly(IC) injection. There were no differences in the proportion of Tbr1-positive postmitotic neurons 48 h after poly(IC) injection. At E18.5, there were more Pax6-positive and Tbr2-positive neural progenitor cells in the poly(IC)-injected group than in the saline-injected group. Gene ontology enrichment analysis of poly(IC)-induced differentially expressed genes in the fetal brain at E12.5 demonstrated that these genes were enriched in terms including response to cytokine, response to decreased oxygen levels in the category of biological process. At E13.5, activating transcription factor 4 (Atf4), which is an effector of integrated stress response, was significantly upregulated in the fetal brain. Our results show that poly(IC)-induced MIA at E12.5 leads to dysregulated neurogenesis and upregulates Atf4 in the fetal brain. These findings provide a new insight in the mechanism of MIA causing improper brain development and subsequent neurodevelopmental disorders.
ASD, autism spectrum disorders; Activating transcription factor 4; Atf4, activating transcription factor 4; CP, cortical plate; DEG, differentially expressed gene; ISR, integrated stress response; Integrated stress response; MIA, Maternal immune activation; Maternal immune activation; NPCs, neural progenitor cells; Neurogenesis; Polyriboinosinicpolyribocytidylic acid; SVZ, subventricular zone; UPR, unfolded protein response; Unfolded protein response; VZ, ventricular zone; [polyI:C], polyriboinosinicpolyribocytidylic acid
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Banco de datos:
MEDLINE
Tipo de estudio:
Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Idioma:
En
Año:
2021
Tipo del documento:
Article