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A multiscale analysis in CD38 −/− mice unveils major prefrontal cortex dysfunctions. une analyse multi-écehelle sur la souris CD38-/- revele des disfonctionnements préfrontaux majeurs
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Edité par CCSD ; Federation of American Society of Experimental Biology -
International audience. 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 Ca 2+-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 2/2 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 neu-romodulators known to control behavioral flexibility, we found elevated monoamine levels in the PFC of CD38 2/2 adult mice. Overall, our study unveiled major changes in PFC physiologic mechanisms and provides new evidence that the CD38 2/2 mouse could be a relevant model to study pathophysiological brain mechanisms of mental disorders such as ASD.-Martucci, L. A multiscale analysis in CD38-/-mice unveils major prefrontal cortex dysfunctions.
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