Transferrin and Thyroid Hormone converge in the control of myelinogenesis

MARZIALI L; FRANCO P; PASQUINI J

Berlin

Congreso; XI European Meeting on Glial Cells in Health and Disease; 2013

Glia

T08-19A Transferrin and Thyroid hormone converge in the control of myelinogenesis L. Marziali1, P. Franco1, J. Pasquini1 1University of Buenos Aires, Caba, Argentina Several humoral factors and others factors originated at the central nervous system (CNS) are needed for myelination in rodents. This implicates that glial precursor cells, once originated at neural stem cells (NSCs) niches differentiate into oligodendroglial precursors (OPCs) and migrate to different brain areas. OPCs finally reach their higher differentiation stage originating mature oligodendrocytes (OLGs) characterized by myelin basic protein (MBP) expression 1. Thyroid hormones (TH: thyroxine [T4], and 3,5,3'- triiodothyronine [T3]) are essential for normal development, growth and metabolism, specially during fetal and early postnatal development. TH effects are mediated by nuclear thyroid hormone receptors (TRs α/β) that have DNA binding properties and are able to regulate gene expression through the recruitment of co-repressors or co-activators in a ligand dependent manner2. Recently, non-classic effects of THs have been described implicating the activation of several signaling cascades through the interaction of T3 and T4 with membrane receptors3. TH is recognized as a pro myelinogenic factor capable of inducing NSCs and OPCs to differentiate into OLGs both in physiological and pathological conditions. Previous results from the laboratory showed that T3 accelerates myelination in vivo in a model of neonatal hyperthyroidism4. Evidence from the laboratory also showed that hyperthyroid state renders an increase in the expression of Transferrin (Tf) mRNA levels and myelin proteins. Other piece of evidence from the laboratory showed that an intracranial injection of apo-Transferrin (aTf) between the third and fifth day of life also has pro myelinogenic effects5. This was explained by aTf ability to induce MBP gene expression in this short period after birth. aTf is also able to increase the expression of TRβ in N20.1 oligodendrocyte cell line6. Since aTf effects in vivo presented a temporal window of action and TH increased Tf mRNA expression, we postulate that TH and Tf could exert a combined control of oligodendrogenesis. In this model, Tf could be commiting NSCs and progenitor cells to the oligodendroglial linage, while TH could be stimulating last steps of differentiation to render mature myelinating OLGs.