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

MARIA INÉS ZALOSNIK FIGUEROA; MARIA LAURA BERTOLDI; ALICIA LAURA DEGANO

Mar del Plata

Congreso; XXX Annual Meeting and SAN-ISN Small Conference and Course; 2015

Sociedad Argentina de Investigacion en Neurociencias

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. To this end we first evaluated the autoimmune response in the context of the experimental autoimmune encephalomyelitis (EAE). Male MeCP2 WT and MT mice, 9 weeks old, were immunized with MOG 35-55 peptide, scored daily for EAE signs and sacrificed at 11 days post induction (dpi; acute stage) or at 56 dpi (chronic stage). When compared WT-EAE animals with MT-EAE animals, we found that MeCP2 MT mice showed accelerated onset of the disease and more severe clinical scores. Coronal sections of spinal cord were subjected to IHC to analyze the occurrence of activated microglia (Iba-1 and CD11-b) and pro-inflammatory cytokines, and to evaluate the presence of cell infiltration. Our results showed a more severe neuroinflammation in the absence of MeCP2; further studies will determine whether Mecp2 affects the generation of autoimmunity and /or the regulation of neuroinflammation.