DEFICITS OF HIPPOCAMPAL STRUCTURAL PLASTICITY IN A MOUSE MODEL OF MECP2 DEFICIENCY

MARIA LAURA BERTOLDI; MARIA INÉS ZALOSNIK FIGUEROA; MARIA CAROLINA FABIO; 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

Methyl citosine binding protein-2 (MeCP2) is a chromosomal structural protein involved in the regulation of gene expression. Alterations in MeCP2 levels have been linked to neurodevelopmental and learning disorders. MeCP2 plays an important role in the maintenance of synaptic connections in the adult nervous system. In the adult hippocampus, the infrapyramidal tract (IPT) undergoes dynamic changes in response to neuronal activity and in addition to adult neurogenesis constitutes important events for pre-synaptic structural plasticity of the hippocampus. In the present work, we aim to define how the lack of MeCP2 interferes with these processes. Using mouse models of MeCP2 deficiency, we found that the volume of the IPT tract increases significantly 2 weeks after kainic-induced seizures in WT mice but not in MeCP2 MT (mutant) mouse. BDNF expression was up-regulated at both 6hrs and 2 weeks after kainic exposure in WT mice, but this increase was detected only after 6hrs in MeCP2 MT mice. Using BrDU injections and IHC we found no defects in kainic-induced adult neurogenesis in MeCP2 MT mice; however, the percentage of granule cells reaching maturity (NeuN+ Calbindin+) was significantly lower in this group. In addition, MT mice showed lower performance in a spatial learning paradigm (Barnes maze). These results shed light about the role of MeCP2 in neural circuit plasticity and learning