Role of MECP2 in neuroimmune interactions

ZALOSNIK MARÍA INÉS; BERTOLDI MARÍA LAURA; FABIO MARÍA CAROLINA; CASTAÑARES CLARA N.; ROTH GERMAN A.; DEGANO ALICIA L.

París

Congreso; 26th Biennial Meeting of the International Society for Neurochemistry and the European Society for Neurochemistry; 2017

ISN

Rett Syndrome is an autism spectrum disorder (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, 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, were immunized with MOG 35-55 peptide, scored daily for EAE symptoms and sacrificed at 12 dpi (acute stage) or at 30 dpi (chronic stage). When WT-EAE animals and MT-EAE animals were compared, we found that MeCP2 MT mice showed an accelerated onset of the disease and more severe clinical scores. Coronal sections of spinal cord were subjected to IHC to analyze the level of expression of Iba1 (microglia) and to assess CNS lymphocyte infiltration during EAE. MeCP2 MT animals showed increased levels of infiltrating cells and microgliosis compared to WT mice; this observation correlated with the individual clinical score reached by each animal. To determine the response of immune cells, we re-stimulated spleen mononuclear cells derived from MeCP2 WT and MT mice with MOG peptide in vitro. Proliferation index and cytokine production was assessed. We observed increased proliferation index in all EAE animals compared to CFA in response to MOG stimulus, with no significant differences between MT and WT MeCP2 mice. Nevertheless, when the cytokine response was analyzed, MT-EAE group showed increased IFN-gamma levels in response to MOG in comparison with WT-EAE animals. Our results showed a more severe neuroinflammation in the absence of MeCP2, suggesting that Mecp2 has an active role in regulating the immune response and maintaining the neuroimmune homeostasis.