Galectin-3 exerts a pro-differentiating and pro-myelinating effect within a temporal window spanning precursors and pre-oligodendrocytes: Insights into the action mechanism.

LAURA THOMAS AND LAURA A. PASQUINI

Mar del Plata

Congreso; LXIII Annual Meeting of Sociedad Argentina de Investigación Clínica (SAIC). LXVI Annual Meeting of Sociedad Argentina de Inmunología (SAI); XLVIII Annual Meeting of Sociedad Argetina de Fisiología (SAFIS); 2018

SAIC-SAFIS-SAI

Galectin-3 (Gal-3) is a chimeric protein whose structure containsunusual tandem repeats of proline and short glycine-rich segments fused onto acarbohydrate recognition domain. Our previous studies using treatment ofoligodendroglial precursors (OPC) with recombinant Gal-3 (rGal-3) during 5 dayswith renewal every two days showed enhanced differentiation and myelinintegrity and function through signaling pathway and actin cytoskeleton modulation.The cytoskeleton is key in OLG maturation, as early OLGprocess extension requires dynamic actin assembly, while subsequent myelinwrapping correlates with actin disassembly, dependent on MPB expression. Theaim of the present work was to evaluate rGal-3 time of action and myelinationcapacity in rGal-3-treated OLG. rGal-3 was administered as a single pulse attreatment day (TD) 0, 2 or 4. OLG treated with rGal-3 atTD0 or TD2 showed higher MBP area and IOD, Erk1/2 deactivation, an increase inpAkt and b-catenin and no changes in PDGFRa. Furthermore, rGal-3 increased the polymerizedactin area, activated 4EB-P1 and increased gelsolin expression in bothtreatments. No significant changes were observed in MBP, Akt or 4EB-P1 in OLG treatedat TD4, although Erk1/2 and 4EB-P1 phosphorylation levels slightly decreasedand gelsolin expression increased. These results indicate rGal-3 exerts a pro-differentiatingeffect within a relatively short time window along OLG maturation, acting onOPC and pre-OLG. Axons simulated through aligned poly-lactic fibers were used toevaluate rGal-3-treated OLG myelination capacity. An increase in MBP IOD wasobserved upon rGal-3 treatment at TD5 and TD10, followed by a reduction in MBParea and F-actin area and IOD at TD15, indicating myelin compaction. Myelinatedfibers were detected at TD15 with vehicle treatment but as early as TD10 withrGal-3 treatment, supporting our previous findings that rGal-3 accelerates OLGdifferentiation. Altogether, these findings indicate that rGal-3 enhancesdifferentiation and myelination acting on OPC and pre-OLG.