Immune responses in a model of autism spectrum disorder (ASD)

MARÍA INÉS ZALOSNIK; MA. LAURA BERTOLDI; ALICIA DEGANO

Huerta Grande, Córdoba

Congreso; XXVIII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencia (SAN); 2013

Sociedad Argentina de Investigación en Neurociencia (SAN).

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. First, we evaluated the presence of autoantibodies against CNS proteins, as well as markers of neuroinflamation in two different mouse models of Rett. While the patterns of CNS autoantibodies change along development (2-7 weeks) for all the groups analyzed, we did not detect striking differences among WT and MeCP2 mutant mice. However, we did observed an increase in activated microglia in MeCP2 mutant mice, suggesting neuroinflammation could be implicated in the neuropathology of this syndrome. Future studies will characterize immune responses at later stages of the disease and how this could affect neuronal development.