Galectin-3 protects the CNS in a model of Cuprizone- induced demyelination.

H. C. HOYOS; L. A. PASQUINI; M. MARDER; J. M. PASQUINI

Baltimore

Congreso; ASN Annual Meeting; 2012

Multiple sclerosis (MS), the most common inflammatory demyelinating CNS disease affecting approximately one million adults, shares the basic pathological hallmark of CNS inflammatory demyelination (Wei Hu & Claudia F. Lucchinetti). MS also produces a significant oligodendrocyte (OLGs) disease. We have previously found that Galectin-3 promotes myelination in CNS by inducing OLG maturation. Here, we hipothesize that Galectin-3 protects CNS from demyelination. Cuprizone (CPZ) induces a reproducible demyelination in the mice brain. The CPZ-induced demyelination is characterized by the OLGs loss, myelin sheats degeneration and astrocytes and microglia recruitment to the lesioned area. Lgals3-/- mice feded from 8 weeks up to 6 weeks of age with CPZ 0.2% w/w. were allowed to remyelinate by removing the CPZ from the diet. CPZ-induced demyelination triggers an exacerbated astrocytic response as well as a microglial infiltration in Lgals3-/- mice vs. WT littermates. Electron microscopy showed a significant lack of myelinated axons in Lgals3-/- mice in comparison to controls. Even though, the few myelinated axons, were nearly 50% less myelinated than controls. Behavioral assays demonstrated lower locomotor activity, decreased levels of anxiety and spatial working memory deficits in Lgals3-/- in comparison with their controls. Our results, seems to demonstrate that Galectin-3 protects the CNS against the CPZ induced-demyelination, strongly supported by the enhanced severity of the injury observed in the myelin of Lgals3-/- treated with CPZ relative to WT mice. Our results allow us probably in the future to suggest Galectin-3 as a terapeutic in MS.