Glial Cells in Health and Disease of the CNS

H. C. Hoyos, Mariel Marder, R. Ulrich, V. Gudi, M. Stangel, G. A. Rabinovich, L. A. Pasquini, J. M. Pasquini, Hoyos, H. C., Marder, Mariel, Ulrich, R., Gudi, V., Stangel, M., Rabinovich, G. A., Pasquini, L. A., Pasquini, J. M.

The aim of this 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, 8-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(Lgals3 (-/-)) and wild type (WT) mice were fed a diet containing 0.2 % CPZ w/w for 6 weeks, after which CPZ was withdrawn in order to allow remyelination.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+, TNFα+ 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.