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

Pangrazzi, L.; Cerilli, E.; Balasco, L.; Tobia, C.; Dall'O', G. M.; Chelini, G.; Perini, S.; Filosi, M.; Ravizza, T.; Vezzani, A.; Provenzano, G.; Pastore, A.; Weinberger, B.; Domenici, E.; Bozzi, Y.

doi:10.1101/2023.09.11.557109

bioRxiv · 10.1101/2023.09.11.557109

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

Pangrazzi, L.·Cerilli, E.·Balasco, L.·Tobia, C.·Dall'O', G. M.·Chelini, G.·Perini, S.·Filosi, M.·Ravizza, T.·Vezzani, A.·Provenzano, G.·Pastore, A.·Weinberger, B.·Domenici, E.·Bozzi, Y.

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Abstract

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 lacking Cntnap2 (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 in Cntnap2-/- 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 in Cntnap2+/+animals. Our findings therefore suggest that the interplay between oxidative stress and inflammation may support ASD-related behaviors in mice.

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Pangrazzi, L., Cerilli, E., Balasco, L., Tobia, C., Dall'O', G. M., Chelini, G., Perini, S., Filosi, M., Ravizza, T., Vezzani, A., Provenzano, G., Pastore, A., Weinberger, B., Domenici, E., Bozzi, Y.. 2023-09-14. The interplay between oxidative stress and inflammation supports autistic-related behaviors in mice. https://doi.org/10.1101/2023.09.11.557109

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