Deficits of hippocampal structural plasticity in a mouse model of MeCP2 deficiency

ZALOSNIK, MARÍA INÉS; DEGANO, ALICIA; FABIO, MARIA CAROLINA; BERTOLDI, MARÍA LAURA; ROTH, GERMAN

Córdoba

Congreso; SAIB 52th meeting; 2016

Methylcitosine binding protein-2 (MeCP2) is a chromosomal structural protein involvedin the regulation of gene expression. Alterations in MeCP2 levels have beenlinked to neurodevelopmental and learning disorders. MeCP2 plays an importantrole in the maintenance of synaptic connections in the adult nervous system.  In the adult hippocampus, the infrapyramidaltract (IPT) undergoes dynamic changes in response to neuronal activity and inaddition to adult neurogenesis constitutes important events for pre-synapticstructural plasticity of the hippocampus. In the present work, we aim to definehow the lack of MeCP2 interferes with these processes. Using mouse models ofMeCP2 deficiency, we found that the volume of the IPT tract increasessignificantly 2 weeks after kainic-induced seizures in WT mice but not in MeCP2MT (mutant) mouse. BDNF expression was up-regulated at both 6hrs and 2 weeksafter kainic exposure in WT mice, but this increase was detected only after6hrs in MeCP2 MT mice. Using BrDU injections and IHC we found no defects inkainic-induced adult neurogenesis in MeCP2 MT mice; however, the percentage ofgranule cells reaching maturity (NeuN+ Calbindin+) wassignificantly lower in this group. In addition, MT mice showed lowerperformance in a spatial learning paradigm (Barnes maze). These results shed light about the role of MeCP2 in neural circuit plasticity and learning.