Remyelination after Cuprizone treatment: Galectin-3 involvement

HOYOS, HERNÁN CARLOS; MARDER, MARIEL; RABINOVICH, GABRIEL ADRIÁN; PASQUINI, LAURA ANDREA; PASQUINI, JUANA MARÍA

Berlin

Congreso; Glia Meeting 2013; 2013

Glia meeting

Cuprizone (CPZ) is a copper chelator which induces reproducible demyelination in the mouse brain (Matsushima and Morell, 2001). CPZ-induced demyelination is characterized by oligodendroglial cell loss, myelin sheath degeneration and astrocyte and microglia recruitment to the lesioned area. The CPZ model causes demyelination without participation of the immunological system. Galectin-3 (Gal-3) is a 31 kDa lectin which binds to -galactosides and is widely spread among different cell types and tissues. We have previously found that Gal-3 is involved in the control of myelin integrity and function and drives oligodendroglial cell differentiation (Pasquini et al., 2011). Remyelination is a regenerative process during which new myelin sheaths wrap axons after pathological demyelination (Fancy et al., 2011). Eight-week-old Lgals3-/- and wild type (WT) mice were fed a diet containing 0.2% CPZ w/w during 6 weeks, after which CPZ was withdrawn in order to evaluate remyelination 2 weeks after. According to our results, CPZ-induced demyelination in Lgals3-/- mice showed an exacerbated astrocytic and microglial response as compared to WT littermates. Electron microscopy showed a significant lack of myelinated axons in Lgals3-/- mice as compared to controls. Furthermore, the few myelinated axons present were nearly 50% less myelinated than those of controls and were found to be collapsed. Remarkably, the remyelination process seemed to be faster in Lgals3-/- mice than in WT. Remyelinated Lgals3-/- mice showed a higher Myelin Basic Protein (MBP) recovery rate as compared to their controls. Flow cytometry assays showed a sharper microglial response in Lgals3-/- mice, which was supported by an exacerbated number of CD11b+ and CD45+ cells. However, electron microscopy images from remyelinated Lgals3-/- animals showed, again, collapsed axons with a defective myelin wrap, as compared to WT mice showing normal axons without any relevant myelin wrap disruption. Behavioral performance observed during CPZ treatment recovery correlates with alterations in the morphological studies, which show that neither Lgals3-/- nor WT mice reach basal myelination levels.