POSTNATAL DEVELOPMENT OF VASOPRESSINERGIC AND OXYTOCINERGIC SYSTEMS AND RELATED SOCIAL AND STEREOTYPED BEHAVIOURS IN A MOUSE MODEL OF RETT SYNDROME

Rett syndrome is a severe neurodevelopmental disorder primarily caused by mutations in the X-linked MECP2 gene and characterized by cognitive and motor impairment. Mouse models of Rett syndrome recapitulate important aspects of the disease, including altered social behaviours and stereotyped and repetitive movements such as excessive grooming. These behaviours are modulated by the nonapeptidergic systems of vasopressin (AVP) and oxytocin (OT), which play a central role in the control of social behaviours, including olfactory recognition in mice. Previous studies in the B6.129.Mecp2-null mouse model for Rett syndrome showed a dysregulation of these neuropeptidergic systems and related social behaviours. Here, we characterized the AVP-ergic and OT-ergic systems longitudinally in a Rett syndrome mouse model derived to a CD1 background. We analysed key developmental stages, including early postnatal life (P12), pubescent stage (P28), and young adulthood (P60), using double immunofluorescence labelling for AVP and OT and analysing brain regions critically involved in social behaviour, including the medial amygdala, ventral lateral septum, and ventral hippocampus. In parallel, we assessed social behaviours by testing investigation of urine chemosignals from different males by means of a habituation-dishabituation test and evaluated self-directed grooming. Our results provide novel information of the postnatal development of nonapeptidergic systems in the mouse model for Rett syndrome and their possible relationship with altered social behaviours. Funded by Funded by Conselleria de Educación, Cultura y Universidades from the Generalitat Valenciana (CIAICO/2023/027; CIAICO/2023/041) and the Spanish Ministry of Science, Innovation and Universities (PID2022-141733NB-I00; MCIU/ AEI /10.13039/501100011033/FEDER, UE).