EARLY INTERLEUKIN-17A BLOCKADE FOLLOWING MATERNAL IMMUNE ACTIVATION CONTRASTS BEHAVIORAL ABNORMALITIES, HIPPOCAMPAL SYNAPTIC CHANGES AND NEUROINFLAMMATION IN MALE AND FEMALE OFFSPRING

Autism Spectrum Disorder (ASD) is characterized by impairments in social communication and interaction, alongside repetitive behaviors, with immune dysregulation involved in its pathogenesis. Preclinical studies indicate that infections during pregnancy and resultant maternal immune activation (MIA) induces ASD-like neurobehavioral abnormalities in offspring, involving interleukin-17A (IL-17A) released by T helper 17 cells. Here, we investigated the potential efficacy of early administration of IL-17A antibody shortly after MIA induction to mitigate ASD-like phenotypes focusing on both male and female mouse offspring.
MIA was induced by administering polyinosinic:polycytidylic acid [Poly(I:C)] to pregnant mice on gestational day 12.5. Twenty-four hours later, mice were injected with IL-17A antibody. Offspring were tested with a tailored behavioral battery relevant to ASD. Additionally, to get further insight into the early MIA-induced molecular changes and the potential efficacy of anti-IL-17A treatment in preventing these effects, hippocampal synaptic and neuroinflammatory markers were analyzed at postnatal day 28.
Prenatal administration of IL-17A antibody significantly attenuated repetitive behaviors selectively observed in MIA male offspring and modulated social deficits emerging in late adolescence in both sexes. Importantly, IL-17A antibody administration prevented in both sexes early MIA-induced alterations in key players of synaptic plasticity (i.e. brain derived neurotrophic factor, synaptic proteins) and neuroinflammation.
Early and precisely timed blockade of IL-17A represents a promising therapeutic strategy to prevent ASD-like brain and behavioral abnormalities associated with MIA.