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,; PASQUINI LA,; PASQUINI JM

ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY.

SPRINGER-VERLAG BERLIN

Año: 2016 vol. 949 p. 311 - 332

0065-2598

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(Lgals3-/-) and wild type (WT) mice were fed a diet containing 0.2% CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination.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.