Poster A93, Saturday, March 25, 5:00 – 7:00 pm, Pacific Concourse
Galectin-3 is a novel negative regulator of memory formation
Hsiao-Yuan Lee1,2, Yan-Chu Chen2, Yun-Li Ma1, Cheng-Hsiung Lin1, Wei-Lun Hsu1; 1Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, 2Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan 114
Galectin-3 is a member of the galectin protein family and it is known to interact with other proteins through recognition of beta-galactoside conjugate on these proteins by its carbohydrate recognition domain. Galectin-3 was found to regulate cell proliferation and inhibit apoptosis. It also plays a pro-inflammatory role and promotes inflammatory responses. But its role in the brain was less studied. Our result showed that galectin-3 expression level is much higher in the hippocampus than in several other brain areas examined in rat. Thus, we studied the role of galectin-3 possibly involved in learning and memory function. Our results revealed that both contextual fear conditioning training and N-methyl-D-aspartate (NMDA) injection to CA1 area dramatically decreased galectin-3 expression in rat hippocampus. Overexpression of galectin-3 impaired fear memory, whereas fear retention and hippocampal long-term potentiation were enhanced in galectin-3 knockout mice. Further, we found that galectin-3 is associated with integrin-alpha3 in rat hippocampus and this association was reduced after fear conditioning training. Moreover, transfection of galectin-3 siRNA to rat CA1 area facilitated fear memory and increased the phosphorylation level of focal adhesion kinase (FAK), but these effects were blocked by co-transfection of the FAK phosphorylation mutant plasmid Flag-FAKY397F. These results together suggest that extracellular galectin-3 impairs fear memory formation through inhibition of integrin-mediated signaling.
Topic Area: LONG-TERM MEMORY: Other