Journal of neuroinflammation · 2018
Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism.
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Wu Yingying, Qi Fangfang, Song Dan, He Zitian, Zuo Zejie, Yang Yunjie, Liu Qiongliang, Hu Saisai, Wang Xiao, Zheng Xiaona, Yang Junhua, Yuan Qunfang, Zou Juntao, Guo Kaihua, Yao Zhibin
Аннотация
BACKGROUND: Prenatal infection is a substantial risk factor for neurodevelopmental disorders such as autism in offspring. We have previously reported that influenza vaccination (VAC) during early pregnancy contributes to neurogenesis and behavioral function in offspring.
RESULTS: Here, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC improves abnormal fetal brain cytoarchitecture and lamination, an effect associated with promotion of intermediate progenitor cell differentiation in MIA fetal brain. These beneficial effects are sufficient to prevent social deficits in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression and attenuates microglial inflammatory responses in the MIA fetal brain.
CONCLUSIONS: Our study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.
RESULTS: Here, we probe the efficacy of VAC pretreatment on autism-like behaviors in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) mouse model. We show that VAC improves abnormal fetal brain cytoarchitecture and lamination, an effect associated with promotion of intermediate progenitor cell differentiation in MIA fetal brain. These beneficial effects are sufficient to prevent social deficits in adult MIA offspring. Furthermore, whole-genome analysis suggests a strong interaction between Ikzf1 (IKAROS family zinc-finger 1) and neuronal differentiation. Intriguingly, VAC rescues excessive microglial Ikzf1 expression and attenuates microglial inflammatory responses in the MIA fetal brain.
CONCLUSIONS: Our study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.
Предметные рубрики MeSH
AnimalsAnimals, NewbornAutistic DisorderCX3C Chemokine Receptor 1Disease Models, AnimalExploratory BehaviorFemaleGene Expression RegulationInfluenza VaccinesLipopolysaccharidesMaleMalformations of Cortical DevelopmentMaze LearningMiceMice, Inbred C57BLMice, TransgenicPregnancyPrenatal Exposure Delayed EffectsSocial Behavior DisordersSwimming