Autism spectrum disorder (ASD) is characterized by early onset of behavioral and cognitive alterations. Low plasma levels of oxytocin (OT) have also been found in ASD patients; recently, a critical role for the enzyme CD38 in the regulation of OT release was demonstrated. CD38 is important in regulating several Ca2+-dependent pathways, but beyond its role in regulating OT secretion, it is not known whether a deficit in CD38 expression leads to functional modifications of the prefrontal cortex (PFC), a structure involved in social behavior. Here, we report that CD38−/− male mice show an abnormal cortex development, an excitation-inhibition balance shifted toward a higher excitation, and impaired synaptic plasticity in the PFC such as those observed in various mouse models of ASD. We also show that a lack of CD38 alters social behavior and emotional responses. Finally, examining neuromodulators known to control behavioral flexibility, we found elevated monoamine levels in the PFC of CD38−/− adult mice. Overall, our study unveiled major changes in PFC physiologic mechanisms and provides new evidence that the CD38−/− mouse could be a relevant model to study pathophysiological brain mechanisms of mental disorders such as ASD.—Martucci, L. L., Amar, M., Chaussenot, R., Benet, G., Bauer, O., de Zélicourt, A., Nosjean, A., Launay, J.-M., Callebert, J., Sebrié, C., Galione, A., Edeline, J.-M., de la Porte, S., Fossier, P., Granon, S., Vaillend, C., Cancela, J.-M., A multiscale analysis in CD38-/- mice unveils major prefrontal cortex dysfunctions. FASEB J. 33, 5823–5835 (2019). www.fasebj.org.
CITATION STYLE
Martucci, L. L., Amar, M., Chaussenot, R., Benet, G., Bauer, O., De Zélicourt, A., … Cancela, J. M. (2019). A multiscale analysis in CD38−/− mice unveils major prefrontal cortex dysfunctions. FASEB Journal, 33(5), 5823–5835. https://doi.org/10.1096/fj.201800489R
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