NOX1/NADPH oxidase affects the development of autism-like behaviors in a maternal immune activation model.
NOX1/NADPH oxidase affects the development of autism-like behaviors in a maternal immune activation model.
复制标题
NOX1/NADPH 氧化酶影响母体免疫激活模型中自闭症样行为的发展。
DOI：
10.1016/j.bbrc.2020.11.070
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发表时间：
2021
期刊：
影响因子：
--
通讯作者：
Katsuyama M and Yabe-Nishimura C.
中科院分区：
文献类型：
--
作者：
Zhang X;Ibi M;Haga R;Iwata K;Matsumoto M;Asaoka N;Liu J;Katsuyama M and Yabe-Nishimura C.
自闭症谱系障碍(ASD)是一种由遗传和环境因素引起的神经发育障碍。在环境因素中，母体感染被认为是ASD的主要危险因素之一。另一方面，死后研究表明氧化应激与ASD的病因有关。然而，氧化应激在ASD发生发展中的作用尚不清楚。在这里，我们报告了NOX1/NADPH氧化酶，一种产生活性氧物种(ROS)的酶，参与了母体免疫激活(MIA)模型中的行为和解剖异常。在妊娠期多聚肌苷-多胞苷(Poly(I：C))暴露的MIA模型中，野生型(WT)和Nox1缺陷小鼠(Nox1KO)的血清IL-6水平均升高。在两种类型的MIA诱导下，在WT的后代中观察到了社会偏好的损害和运动协调的缺陷，但在NOx1基因缺陷的后代中没有观察到。MIA上调了胎儿大脑皮层和小脑中NOX1mRNA的表达，但在成年后代中则不表达。尽管MIA对这两种基因的皮质神经元发育均无影响，但Nox1KO显著改善了受MIA影响的子代第VII小叶中浦肯野细胞的脱落。综上所述，这些结果提示，NOX1/NADPH氧化酶在ASD的某些行为表型中起重要作用，可能是通过促进小脑浦肯野细胞的丢失。
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) andNox1-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 inNox1. 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.
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烟酰胺腺嘌呤二核苷酸磷酸还原型（NADPH）氧化酶NOX1促进星状细胞增殖并加重胆管结扎引起的肝纤维化。
DOI：
--
发表时间：
--
期刊：
Hepatology in press.
影响因子：
--
作者：
Cui W;Matsuno K;Iwata K;Ibi M;Matsumoto M;Zhang J;Zhu K;Katsuyama M;Torok NJ;Yabe-Nishimura C.
通讯作者：
Yabe-Nishimura C.
影响因子：
11
作者：
Wong, C. C. Y.;Meaburn, E. L.;Ronald, A.;Price, T. S.;Jeffries, A. R.;Schalkwyk, L. C.;Plomin, R.;Mill, J.
通讯作者：
Mill, J.
影响因子：
5.3
作者：
Suzuki, Lucia;Coulon, Patrice;Ruigrok, Tom J. H.
通讯作者：
Ruigrok, Tom J. H.
影响因子：
5.9
作者：
Le Belle, Janel E.;Sperry, Jantzen;Ngo, Amy;Ghochani, Yasmin;Laks, Dan R.;Lopez-Aranda, Manuel;Silva, Alcino J.;Kornblum, Harley I.
通讯作者：
Kornblum, Harley I.
影响因子：
6.1
作者：
Reith, R. Michelle;McKenna, James;Gambello, Michael J.
通讯作者：
Gambello, Michael J.