NEUROINFLAMMATORY RESPONSES IN A MOUSE MODEL OF AUTISM SPECTRUM DISORDER (ASD)

MARIA INÉS ZALOSNIK FIGUEROA; MARIA LAURA BERTOLDI; MARIA CAROLINA FABIO; CLARA N CASTAÑARES; ROTH, GERMAN ALFREDO; ALICIA L. DEGANO

Córdoba

Congreso; LII Reunión Anual Sociedad Argentina de Investigación en Bioquímica y Biología Molecular; 2016

Sociedad Argentina de Investigación en Bioquímica y Biología Molecular

Rett Syndrome is an ASD caused by mutations in Methyl Cytosine Binding Protein 2 (MeCP2). Our main goal is to use a mouse monogenic model of ASD, which shows a highly reproducible phenotype, to evaluate the role of altered immunity in the pathogenesis of this disorder. We first evaluated the autoimmune/neuroinflammatory response in the context of the experimental autoimmune encephalomyelitis (EAE). Male MeCP2 WT and MeCP2 mutant (MT) mice were immunized with MOG35-55 peptide to induce EAE, scored daily for clinical signs and sacrificed at 12 dpi (acute stage) or at 56 dpi (chronic stage). MeCP2 MT mice showed an accelerated onset of the disease and more severe clinical scores than WT mice. IHC was performed in sections of spinal cord to detect activated microglia (Iba-1+) and to assess infiltration of immune cells into the CNS. At 12 dpi, cellular infiltrates in spinal cord were higher in MT-EAE than in WT-EAE mice. Also, isolated spleen lymphocytes were re-stimulated with MOG in vitro and cytokine production was assessed. We found high levels of pro-inflammatory cytokines (IL-6, IL-17, IFN) in both MT and WT EAE groups. Our results showed a more severe EAE clinical manifestations as well as neuro inflammatory response in the absence of MeCP2. Ongoing studies are addressing the specific role of Mecp2 in these immune processes.