CONICET Doctoral Fellow / Assistant Professor A (DS) UNC
Director: Alicia Degano
PhD Thesis Topic
Immune responses in a model of autism spectrum disorder (ASD)
Autism spectrum disorders (ASD) consist of a heterogeneous group of neurodevelopmental disorders defined behaviorally by abnormalities in social, verbal, and nonverbal communication. It is widely agreed that a subset of patients with ASD show abnormal immunity. Furthermore, it has been proposed that autoimmunity may play a role in the pathogenesis of ASD. However, immune findings in ASD patients are often inconsistent likely due to the heterogeneous, behavior-defined subject groups.
Rett Syndrome is an ASD caused by mutations in Methyl Cytosine Binding Protein 2 (MECP2) and mouse models of Rett have been widely used for studying ASDs. The main goal of our project is to use this monogenic model of ASD, which shows a highly reproducible pathologic phenotype, in order to evaluate the role of altered immunity in the pathogenesis of this disorder. In particular, first we aim to characterize the production of immune mediators (autoimmune and inflammatory) in mice mutant for MeCP2 at the level of the Central Nervous System (CNS) at pre and post systematic stages. Besides, we want to analyze the effect of immune mediators (like autoantibodies and cytokines) from mutant mice, on the synaptogenesis, dendritic arborization and dendritic spines using neuronal cultures; and on the progression of symptoms and typical behaviors seen in this animal model of ASD.