Galectin-3 participates in the Cuprizone-induced demyelination

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

Québec, QB.

Congreso; 5th Annual Canadian Neuroscience Meeting; 2011

Canadian Association for Neuroscience

Galectin-3 is widely spread among different types of cells and tissues. Through specific interactions with a variety of intra- and extracellular proteins galectin-3 is involved in different physiological and pathophysiological processes. We showed that galectin-3 is up-regulated during oligodendroglial (OLG) differentiation. Moreover, recombinant galectin-3 treatment promotes OLG maturation evidenced by an increased number of MBP+cells and a decrease in A2B5+cells. Accordingly, conditioned media from galectin-3-expressing, but not galectin-3-deficient(Lgals3-/-) microglia, successfully promoted OLG differentiation. Morphometric analysis showed a significant decrease of myelinated axons, myelin turns and g-ratio in the striatum of Lgals3-/- vs WT mice. Cuprizone(CPZ) induces reproducible demyelination in mouse brain. The extent of the CPZ-induced demyelination is characterized by the loss of OLG, myelin sheath degeneration and recruitment of microglia and astrocytes to the lesioned area. We evaluated the susceptibility to CPZ-induced demyelination of 8-week-old-Lgals3-/- vs WT mice. Lgals3-/- mice displayed a decreased myelination evaluated by the number of APC+cells and MBP immunostaining in striatum, corpus callosum(CC), cingulum(CG) and cortex(CX) accompanied by an increase in astroglial activation in CG and microglial response in CC and CG. An increased susceptibility to CPZ-induced demyelination was obtained in Lgals3-/- mice determined by the evaluation of thick horz (average MBP immunostaining) in CX, astroglial response in CC, and APC+ cells in CG at 6 weeks and in eryochrome staining at 4 weeks of treatment. Strikingly, a decreased microglial response to CPZ diet was observed in Lgals3-/- vs WT mice. Our results indicate that galectin-3 participates protecting to the OLG cells against CPZ-induced demyelination.