Is DMT1 involved in myelination?

MARTINEZ VIVOT R; USACH V; GOITIA B; SETTON PC

Congreso; XXVII Congreso Anual de la Sociedad Argentina de Investigación en Neurociencias; 2012

Loss of axonal contact in isolated Schwann cells (SC) in vitro or after nerve injury in vivo leads to de-differentiation of these cells. We have described that holotransferrin (hTf) and iron prevented this de-differentiaton while apotransferrin was unable to avoid it; plus, after iron treatment, intracellular signals towards differentiation become activated. Iron and hTf effect suggests their participation in the axonal signal that enables SC maturation and survival. Whereas Tf-mediated iron uptake is considered the main route, there is evidence for Tf-independent mechanisms. In the present work we demonstrate the existence of a divalent metal transporter (DMT1) greatly described in literature as an iron metabolism key player, but never before within the PNS context. The presence of DMT1 was demonstrated in sciatic homogenate, isolated rat myelin and cultured SC by Western Blot and confirmed through its co-localization with S-100 by immunocytochemistry. In addition, the existence of its mRNA was verified by RT-PCR. DMT1 mRNA was found all along the SC progeny. The determinations were performed in sciatic nerves of rats previously submitted to crush; DMT1 expression was increased 14 days post injury (PI); at 21 and 35 days PI levels did not return to control ones. These data lead us to postulate DMT1 involvement in ensuring the provision of iron in the PNS and to confirm the existence of a Tf independent iron uptake mechanism, validating the role of iron in the axonal signal.