The interplay between oxidative stress and inflammation supports autistic-related behaviors in Cntnap2 mutant mice

Autism Spectrum Disorder (ASD) is a highly prevalent neurodevelopmental condition characterized by social communication deficits and repetitive/restricted behaviors. Several studies showed that inflammation may contribute to ASD. Here we used RT-qPCR, RNA sequencing, immunohistochemistry, and flow cytometry to show that pro-inflammatory molecules were increased in the cerebellum and periphery of mice lackingCntnap2(Cntnap2-/-), a robust model of ASD. In parallel, oxidative stress was present in the cerebellum of mutant animals. Systemic treatment with N-acetyl-cysteine (NAC) rescued cerebellar oxidative stress and inflammation as well as motor and social impairments inCntnap2-/-mice. This was accompanied by improved function of microglia cells in NAC-treated mutant animals. Intriguingly, social deficits, cerebellar inflammation and microglia dysfunction were induced by NAC inCntnap2+/+animals. Our findings therefore suggest that the interplay between oxidative stress and inflammation may support ASD-related behaviors in mice. The experiment is based on cerebellar tissue extracted from CNTNAP2 ko mice sacrificed at different ages; Samples (S) go from 1 to 39 that constituted height groups composed of 5 paired-end samples or biological replicates (except one group with four (4) samples), each sample have been sequenced on two lanes (L001 and L002): 1. S1-S5 WT-AD-F samples 2. S6-S10 WT-AD-M samples 3. S11-S15 KO-AD-F samples 4. S16-S19 KO-AD-M samples (this is the only group with 4 samples) 5. S20-S24 WT-P30-M samples 6. S25-S29 WT-P30-F samples 7. S30-S34 KO-P30-M samples 8. S35-S39 KO-P30-F samples