THE ROLE OF GALECTIN-3: FROM OLIGODENDROGLIAL DIFFERENTIATION AND MYELINATION TO DEMYELINATION AND REMYELINATION PROCESSES IN A CUPRIZONE-INDUCED DEMYELINATION MODEL

HOYOS HC, ; MARDER M, ; ULRICH R, ; GUDI V, ; STANGEL M, ; RABINOVICH GA, MALDONADO CA, KOGAN Z, NIVELONI S, SAMBUELLI A, VAZQUEZ H, PEDREIRA S, SMECUOL E, NEGREIRA S, QUINTAR A, MAZURE R, MAURIÑO E, BAI JC; PASQUINI LA ; PASQUINI JM

Glial Cells in Health and Disease

Springer

Año: 2016;

Abstract The aim of the present work was to combine our previously published results with our new data to show how galectin-3 (Gal-3) controls myelin integrity and function, promotes oligodendroglial cell differentiation and regulates microglial responses to limit cuprizone- (CPZ)-induced demyelination and foster remyelination. In this study, eight-week-old Gal-3-deficient (Lgals3-/-) and wild type (WT) mice were fed a diet containing 0.2% CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination. Our results show that remyelination was less efficient in Lgals3-/- than in WT mice. Electron microscopic images from remyelinated sections in Lgals3-/- mice revealed collapsed axons with a defective myelin wrap, while remyelinated WT mice had normal axons without relevant myelin wrap disruption. MMP-3 expression increased during remyelination in WT but not in Lgals3-/- mice. The number of CD45+, TNF+ and TREM-2b+ cells decreased only in WT mice only, with no alterations in Lgals3-/- mice during demyelination and remyelination. Therefore, Gal-3 influences remyelination by mechanisms involving the tuning of microglial cells, modulation of MMP activity, and changes in myelin architecture.