Disorders of the Nervous System
Author: Jessica Lorena Presa | Email: ib.jpresa@gmail.com
Jessica Lorena Presa1°2°, Carlos Pomilio1°2°, Ángeles Vinuesa, M. Eugenia Matzkin1°, Mariano Soiza-Relly4°, Agustina Alaimo3°, Soledad Gori2°, Juan Beauquis1°2°, Gabriel A. Rabinovich1°, Flavia E. Saravia1°2°
1° IBYME-CONICET
2° Depto de Química Biológica, FCEN, UBA
3° INQUIBICEN, UBA-CONICET
4° IFYBINE, UBA-CONICET
Alzheimer’s disease (AD) is a major public health challenge, with no cure and increasing prevalence. Vascular changes in AD correlate with disease progression, making them a key target for intervention. Galectins, a family of galactoside-binding proteins, are involved in survival, immune, and vascular pathways. We treated 12 m.o PDAPPJ20 mice, an AD model, with 9 i.p. injections of Gal1 (100 µg/dose) or vehicle. Tg mice showed high vascular amyloid deposits in the hippocampal hilus, a vulnerable region in AD. Gal1 reduced these deposits by 35% (p<0.05) without altering vascular density. Astrocyte-endothelial contact, crucial for blood-brain barrier integrity and Aβ clearance, was reduced in Tg mice but restored in Tg-Gal1 mice (lectin staining and GFAP IF). AQP4, an astrocytic endfeet protein necessary for fluid exchange through the BBB, also showed recovery in Tg-Gal1 mice which was diminished in Tg (p<0.02) in an array tomography analysis. We also assessed BBB integrity with i.v. Evans blue. Tg-Gal1 mice showed less vascular permeability to the dye than Tg-Veh mice(p<0.05). In vitro, we used human brain endothelial cells to model the blood-brain barrier. Exposure to 24h of Aβ 1-40 0.1 µM reduced the monolayer's electrical resistance, while Gal1(15 µg/µl) prevented this disruption. Gal1 also mitigated proteostasis alterations in the UPR pathway and proinflammatory activation in endothelial cells caused by Aβ. Our results suggest Gal1 as a potential therapeutic agent for AD.