Maternal Inflammation Contributes to Brain Overgrowth and Autism-associated Behaviors Through Altered Redox Signaling in Stem and Progenitor Cells

Overview

Journal Stem Cell Reports

Publisher Cell Press

Specialty Cell Biology

Date 2014 Nov 25

PMID 25418720

Citations 49

Authors

Janel E Le Belle

Jantzen Sperry

Amy Ngo

Yasmin Ghochani

Dan R Laks

Manuel Lopez-Aranda

Alcino J Silva

Harley I Kornblum

Affiliations

Soon will be listed here.

Abstract

A period of mild brain overgrowth with an unknown etiology has been identified as one of the most common phenotypes in autism. Here, we test the hypothesis that maternal inflammation during critical periods of embryonic development can cause brain overgrowth and autism-associated behaviors as a result of altered neural stem cell function. Pregnant mice treated with low-dose lipopolysaccharide at embryonic day 9 had offspring with brain overgrowth, with a more pronounced effect in PTEN heterozygotes. Exposure to maternal inflammation also enhanced NADPH oxidase (NOX)-PI3K pathway signaling, stimulated the hyperproliferation of neural stem and progenitor cells, increased forebrain microglia, and produced abnormal autism-associated behaviors in affected pups. Our evidence supports the idea that a prenatal neuroinflammatory dysregulation in neural stem cell redox signaling can act in concert with underlying genetic susceptibilities to affect cellular responses to environmentally altered cellular levels of reactive oxygen species.

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