Neuroinflammatory responses in a mouse model of Autism Spectrum Disorder (ASD)

FABIO, MARIA CAROLINA; DEGANO, ALICIA; CASTAÑARES, C.N.; ZALOSNIK, MARÍA INÉS; ROTH, GERMAN

Córdoba

Congreso; SAIB 52th meeting; 2016

SAIB

Rett Syndrome is an ASD caused by mutations in MethylCytosine Binding Protein 2 (MeCP2). Our main goal is to use a mouse monogenicmodel of ASD, which shows a highly reproducible phenotype, to evaluate the roleof altered immunity in the pathogenesis of this disorder. We first evaluatedthe autoimmune/neuroinflammatory response in the context of the experimentalautoimmune encephalomyelitis (EAE). Male MeCP2 WT and MeCP2 mutant (MT) mice wereimmunized with MOG35-55 peptide to induce EAE, scored daily for clinical signsand sacrificed at 12 dpi (acute stage) or at 56 dpi (chronic stage). MeCP2 MTmice showed an accelerated onset of the disease and more severe clinical scoresthan WT mice. IHC was performed in sections of spinal cord to detect activatedmicroglia (Iba-1+) and to assess infiltration of immune cells intothe CNS. At 12 dpi, cellularinfiltrates in spinal cord werehigher in MT-EAE than in WT-EAE mice. Also, isolated spleen lymphocytes were re-stimulated withMOG in vitro and cytokine production was assessed. We found high levels ofpro-inflammatory cytokines (IL-6, IL-17, IFNg) in both MT and WT EAE groups. Our results showed amore severe EAE clinical manifestations as well as neuro inflammatory responsein the absence of MeCP2. Ongoing studies are addressing the specific role of Mecp2in these immune processes.