Galectin-1-induced cognitive improvement, lower vascular and parenchymal amyloid deposition and immunomodulation in an animal model of Alzheimer's disease

JUAN BEAUQUIS; JÉSICA PRESA; FLAVIA E. SARAVIA; ANGELES VINUESA; ROSA MORALES; CARLOS POMILIO; MELISA BENTIVEGNA; GABRIEL RABINOVICH

Congreso; BRAIN 2017; 2017

Alzheimer's disease (AD) is the leading cause of dementia in the elderly. Amyloid deposition and neuroinflammation are recognized hallmarks in AD, affecting mainly the brain cortex and hippocampus, both in patients and animal models. Galectin-1 (Gal1) -a glycan binding protein- is proposed to modulate several properties on immune and endothelial cells. Rabinovich's group (1) has previously reported a Gal1 neuroprotective role through deactivation of microglia in experimental autoimmune encephalitis, inducing an alternative phenotype. Here, we administered Gal1 or vehicle (i.p. 9 injections of 100ug/dose) during 3 weeks to 12-month-old PDAPPJ20 transgenic mice (Tg), or age-matched non-transgenic animals. Gal1 treatment improved the performance in the novel object location recognition test (p< 0.05). Congo red amyloid+ area in the hippocampus was decreased by 50% (p< 0.05) affecting mainly the dorsal hippocampus. Iba1+ microglial cells in the dentate gyrus exhibited less reactivity measured as soma size after Gal1 treatment (p< 0.05) while morphological score of microglial activation was significantly reduced, suggesting a modulatory effect on this cell population involved in amyloid clearance through phagocytosis. Moreover, the perivascular amyloid deposition decreased in treated Tg mice, visualized by tomato lectin labeling for microvasculature combined with Aβ immunofluorescence. In addition, we found that GFAP+ astrocytes surrounding amyloid plaques were Gal1+ in the hippocampus of Tg mice. We also generated PDAPPJ20/Gal1-/- animals, which exhibited an increased number of Iba1+ cells in the hippocampus. Our results showed a potential relevant role for Gal1 in this neurodegenerative disease at multiple levels, including cellular and cognitive aspects. Additional in vitro experiments are in progress to identify the associated mechanism of action of Gal1 modulating the neuroinflammatory status in the context of AD.