Contribution of MeCP2 and synaptic activity to hippocampal structural plasticity

MARIA LAURA BERTOLDI; MARIA INÉS ZALOSNIK FIGUEROA; ALICIA LAURA DEGANO

Mar del Plata

Congreso; XXX Annual Meeting and SAN-ISN Small Conference and Course; 2015

Sociedad Argentina de Investigacion en Neurociencias

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. Recent work indicates that removal of MeCP2 in adult animals also induce neurologic defects suggesting a role in the maintenance of synaptic connections in the adult nervous system. In the adult hippocampus, the infrapyramidal tract (IPT) undergoes dynamic changes in size in response to neuronal activity, and together with 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 mutant mouse. However, using BrDU injections and IHC we found no defects in kainic-induced adult neurogenesis in MeCP2 mutant mice, suggesting a defect in the maturation or axonal guidance of the new neurons in the absence of MeCP2.In addition, we found that BDNF expression was up-regulated at both 6hrs and 2 weeks after kainic exposure in WT mice, but it was increased only after 6hrs in MeCP2 mutant mice. This finding suggests that the sustained increase of BDNF expression may play a role in the dynamic growth of IPT in response to neuronal activity.