MYELIN-ASSOCIATED GLYCOPROTEIN MODULATES PROGRAMMED CELL DEATH OF MOTONEURONS DURING DEVELOPMENT

PALANDRI, ANABELA; ROZÉS SALVADOR, VICTORIA; RONALD L. SCHNAAR; PABLO HECTOR HORACIO LOPEZ

Ciudad Autónoma de Buenos Aires

Workshop; WorkshopFronteras en Biociencia; 2012

Agencia Nacional de Promoción Científica y Tecnológica

Myelin-associated glycoprotein (MAG) is a lectin present in the periaxonal layer of myelin that engages several axonal receptors, including Nogo-receptors (NgRs), to mediate its biological functions. It has been proposed that NgRs have a modulatory role on programmed cell death (PCD) of motoneurons (MNs) dependent of the neurotrophin receptor P75NTR. The aim of this study was to analyze a possible modulatory role of MAG on PCD of MNs. A time course study showed that early after birth Mag-null mice have a reduction in MNs count. Also Mag-null mice exhibit increased susceptibility in an in vivo model of PCD induced by a sciatic nerve crush. Interestingly pre-treatment with a soluble form of MAG (MAG-Fc) prevented MN apoptosis in this model. Studies using an in vitro model of P75NTR-dependent PCD on spinal cord organotypic cultures and a MN cell line confirmed the protective role of MAG. We further confirmed in in vivo and in vitro models of PCD that the protective effect of MAG was dependent on the activation of the RhoA-signaling pathway. Overall these results demonstrate a new role for MAG as protecting MNs from PCD. These results expand our knowledge of the nurture role of myelination on axons and at the same time open new possibilities for therapeutic intervention.