Exogenous IL-17A Alleviates Social Behavior Deficits and Increases Neurogenesis in a Murine Model of Autism Spectrum Disorders

Author:

Willinger Yehoshua1,Friedland Cohen Daniella R.1,Turgeman Gadi12ORCID

Affiliation:

1. Department of Molecular Biology, Faculty of Natural Sciences, Ariel University, Ariel 40700, Israel

2. The Adelson School of Medicine, Ariel University, Ariel 40700, Israel

Abstract

Among the proposed mechanisms for autism spectrum disorders (ASD) is immune dysregulation. The proinflammatory cytokine Interleukine-17A (IL-17A) was shown to play a key role in mediating immune-related neurodevelopmental impairment of social behavior. Nevertheless, post-developmental administration of IL-17A was found to increase social behavior. In the present study, we explored the effect of post-developmental administration of IL-17A on ASD-like behaviors induced by developmental exposure to valproic acid (VPA) at postnatal day 4. At the age of seven weeks, VPA-exposed mice were intravenously injected twice with recombinant murine IL-17A (8 μg), and a week later, they were assessed for ASD-like behavior. IL-17A administration increased social behavior and alleviated the ASD-like phenotype. Behavioral changes were associated with increased serum levels of IL-17 and Th17-related cytokines. Exogenous IL-17A also increased neuritogenesis in the dendritic tree of doublecortin-expressing newly formed neurons in the dentate gyrus. Interestingly, the effect of IL-17A on neuritogenesis was more noticeable in females than in males, suggesting a sex-dependent effect of IL-17A. In conclusion, our study suggests a complex role for IL-17A in ASD. While contributing to its pathology at the developmental stage, IL-17 may also promote the alleviation of behavioral deficits post-developmentally by promoting neuritogenesis and synaptogenesis in the dentate gyrus.

Publisher

MDPI AG

Subject

Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis

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