Prenatal influenza vaccination rescues impairments of social behavior and lamination in a mouse model of autism

Abstract

BackgroundPrenatal 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.ResultsHere, 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.ConclusionsOur study implies that a preprocessed influenza vaccination prevents maternal bacterial infection from causing neocortical lamination impairments and autism-related behaviors in offspring.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1252-z) contains supplementary material, which is available to authorized users.

Poly(I:C) Challenge Alters Brain Expression of Oligodendroglia-Related Genes of Adult Progeny in a Mouse Model of Maternal Immune Activation

“…Specifically, we exposed pregnant mice to poly(I:C), a synthetic mimetic of viral dsRNA analog, a well-documented mouse model of MIA. We and others have reported that poly(I:C)-induced MIA precipitates altered brain and behavioral phenotypes in offspring that mirror abnormalities observed in ASD and related neurodevelopmental conditions such as schizophrenia (Meyer et al, 2006 ; Li et al, 2015 ; Wei et al, 2016 ; Wu et al, 2018 ).…”

Structural and Functional Deviations of the Hippocampus in Schizophrenia and Schizophrenia Animal Models

“…Therefore, MIA models for schizophrenia frequently induce an activation of the maternal immune response by prenatal injections with immunostimulants like polyinosinic–polycytidylic acid (Poly I:C) or lipopolysaccharide (LPS). The most common cognitive and behavioral abnormalities in these models were observed for parameters like prepulse inhibition [ 191 , 192 , 193 , 194 , 195 , 196 , 197 ], latent inhibition [ 195 , 198 ] and social interaction [ 193 , 199 , 200 ]. In rhesus monkeys, a Poly I:C-induced maternal immune challenge increased repetitive behavior patterns and reduced communication, as well as social interactions in the offspring [ 201 ].…”

Impact of maternal immune activation on dendritic spine development

“…Thus, their contribution to both the acute and long-term effects of prenatal immune insult might be particularly important. Indeed, many MIA protocols resulted in changes in microglial density and activation states in offspring in various brain regions that were observed already in the embryonic stage (Wu et al, 2018), shortly after birth (Li et al, 2014), and in adulthood (Hadar et al, 2017;Van den Eynde et al, 2014;Zhu et al, 2014). However, in other studies, these differences were not detected (Corradini et al, 2018;Garay et al, 2013;Giovanoli et al, 2015Giovanoli et al, , 2016.…”