Gal-1 participates in demyelination process through its capacity to activate astrocytes and induce bdnf expression

PASQUINI, L.A.; MILLET , V; RABINOVICH, G.; PASQUINI, J.M.

Santa Fe, New Mexico, EEUU

Congreso; ASN 2010, 41st Annual meeting; 2010

American Society of Neurochemistry

Gal-1 is the first identified member of the galectin family of carbohydrate-binding proteins that has been implicated in a variety of biological events. Our results and those reported by other authors have demonstrated that Gal-1 is expressed mainly in astrocytes and induces differentiation of these cells leading to BDNF production. BDNF expression increases in acute injuries and decreases in chronic lesions in MS and EAE model. Exogenous administration of BDNF reduces EAE severity and it was suggested to enhance remyelination in CNS and PNS. We studied the participation of Gal-1 in demyelination process. We used the cuprizone (CPZ) model in 129sv Gal1-/- and Gal1+/+ mice and in C57BL-6 transgenic mice expressing EGFP upon the promoter of a characteristic oligodendroglial marker, CNPase, evaluated in the 3rd and 5th week of CPZ diet. Time dependent demyelination was observed in CNP-EGFP mice fed with 0.2% CZP. We also obtained a decrease in BDNF expression in the SVZ and changes in the cortical profile in 129sv and C57BL-6. 129sv mice resulted less susceptible than C57BL-6 to CPZ induced demyelination in the corpus callosum and cortex in the 5th week of intoxication analysed by MBP immunohistochemistry. We have also observed a decrease in basal cortical myelination in Gal1-/- and a higher demyelination in response to CPZ diet relative to Gal1 +/+. Levels of astroglial activation were decreased in Gal1 -/- mice regard to Gal1+/+ submitted to CPZ diet. Interestingly, we obtained decreased levels of BDNF expression in Gal-/- relative to Gal+/+ in response to CPZ diet. Our results indicate that Gal-1 might be involved in demyelination process through its capacity to activate astrocytes and induce BDNF expression.