Ricerc@Sapienza

Autism Spectrum Disorders (ASDs) are neurodevelopmental syndromes, characterized by behavioral deficits and a strong genetic background.
The complex etiology underlying these disorders relies on both environmental and genetic factors. Among the chromosomal alterations found in ASDs patients, the R451C substitution in the synaptic protein Neuroligin3 (NLGN3) has been highly characterized. We have previously shown that the mutation affects folding of the extracellular protein domain, causing its retention in the Endoplasmic Reticulum (ER), while only a residual ~10% of the mutant protein is reaching the synapse. The mutation inserted in the endogenous gene in vivo, in the mouse model R451C NLGN3, has been shown to cause alterations in neurotransmission in several brain areas along with an autistic behavioural phenotype characterized by repetitive behaviors. The fraction of mutant protein retained in the ER causes a stress condition in the organelle and the activation of the Unfolded Protein Response (UPR) in vitro and in vivo.
Recently, the pro-social hormone oxytocin (OXT) has received considerable attention for research into the etiology and treatment of ASDs. To date, a large number of evidences support a role of OXT in the development of social skills and in the reduction of repetitive behaviors, typical traits of ASDs. Recent studies have highlighted alterations in the oxitoninergic system both in patients with ASDs and in mouse models of neuropsychiatric pathologies.
The aim of this project is to further characterize the effect of OXT on alleviating the stress condition in the ER and recovering the autistic phenotype in the monogenic mouse model of autism, expressing the R451C mutation in NLGN3 as endogenous protein.