NOX1/NADPH oxidase affects the development of autism-like behaviors in a maternal immune activation model.

Abstract

Autism spectrum disorder (ASD) is a neurodevelopmental disorder caused by genetic and environmental factors. Among the environmental factors, maternal infection is known as one of the principal risk factors for ASD. On the other hand, postmortem studies suggested the relationship of oxidative stress with ASD etiology. However, the role of oxidative stress in the development of ASD remains unclear. Here, we report the involvement of NOX1/NADPH oxidase, an enzyme generating reactive oxygen species (ROS), in behavioral and anatomical abnormalities in a maternal immune activation (MIA) model. In the MIA model of gestational polyinosinic-polycytidylic acid (poly(I:C)) exposure, increased serum levels of IL-6 were observed in both wild-type (WT) and Nox1-deficient mice (Nox1KO). Following the comparable induction of MIA in the two genotypes, impairment of social preference and defects in motor coordination were observed in WT offspring but not in offspring deficient in Nox1. MIA up-regulated NOX1 mRNA in the cerebral cortex and cerebellum of the fetus but not in the adult offspring. Although the development of cortical neurons was unaffected by MIA in either genotype, the dropout of Purkinje cells in lobule VII of MIA-affected offspring was significantly ameliorated in Nox1KO. Taken together, these results suggested that NOX1/NADPH oxidase plays an essential role in some behavioral phenotypes observed in ASD, possibly by promoting the loss of Purkinje cells in the cerebellum.

• Authors: Xueqing Zhang, Masakazu Ibi, Ryu Haga, Kazumi Iwata, Misaki Matsumoto, Nozomi Asaoka, Junjie Liu, Masato Katsuyama, Chihiro Yabe-Nishimura
• Journal: Biochemical and biophysical research communications (Biochem Biophys Res Commun) Vol. 534 Pg. 59-66 (01 01 2021) ISSN: 1090-2104 [Electronic] United States
• PMID: 33310189 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 Elsevier Inc. All rights reserved.

Chemical References

• NADPH Oxidase 1
• NOX1 protein, mouse
• Poly I-C

Topics

• Animals
• Autism Spectrum Disorder (etiology, immunology)
• Behavior, Animal (physiology)
• Cerebellum (embryology)
• Cerebral Cortex (embryology)
• Disease Models, Animal
• Female
• Gene Expression Regulation, Developmental
• Male
• Mice, Inbred C57BL
• Mice, Knockout
• NADPH Oxidase 1 (genetics, metabolism)
• Poly I-C (immunology, pharmacology)
• Pregnancy
• Purkinje Cells (pathology)
• Mice