Abstract
Galectin-3, a member of the galectin protein family, has been found to regulate cell proliferation, inhibit apoptosis and promote inflammatory responses. Galectin-3 is also expressed in the adult rat hippocampus, but its role in learning and memory function is not known. Here, we found that contextual fear-conditioning training, spatial training or injection of NMDA into the rat CA1 area each dramatically decreased the level of endogenous galectin-3 expression. Overexpression of galectin-3 impaired fear memory, whereas galectin-3 knockout (KO) enhanced fear retention, spatial memory and hippocampal long-term potentiation. Galectin-3 was further found to associate with integrin α3, an association that was decreased after fear-conditioning training. Transfection of the rat CA1 area with small interfering RNA against galectin-3 facilitated fear memory and increased phosphorylated focal adhesion kinase (FAK) levels, effects that were blocked by co-transfection of the FAK phosphorylation-defective mutant Flag-FAKY397F. Notably, levels of serine-phosphorylated galectin-3 were decreased by fear conditioning training. In addition, blockade of galectin-3 phosphorylation at Ser-6 facilitated fear memory, whereas constitutive activation of galectin-3 at Ser-6 impaired fear memory. Interestingly galectin-1 plays a role in fear-memory formation similar to that of galectin-3. Collectively, our data provide the first demonstration that galectin-3 is a novel negative regulator of memory formation that exerts its effects through both extracellular and intracellular mechanisms.
Highlights
Galectin-3 is a member of the galectin protein family—a large family of animal lectins whose members produce various biological effects (Barondes et al, 1994b) by interacting with other proteins through recognition of a β-galactoside conjugate on these proteins by the galectin carbohydrate-recognition domain (CRD; Barondes et al, 1994a)
These analyses indicated that the expression level of galectin-3 is approximately 2.5–6fold higher in the hippocampus than in other areas examined, including the frontal cortex, olfactory bulb, striatum and amygdala (Figures 1A,B, middle panel)
To confirm that the above alteration of hippocampal galectin-3 expression was caused by training-induced neuronal activation, we further examined the effect of NMDA injection (12.5 mM) into the rat CA1 area on galectin-3 expression; control animals received an injection of phosphate-buffered saline (PBS)
Summary
Galectin-3 is a member of the galectin protein family—a large family of animal lectins whose members produce various biological effects (Barondes et al, 1994b) by interacting with other proteins through recognition of a β-galactoside conjugate on these proteins by the galectin carbohydrate-recognition domain (CRD; Barondes et al, 1994a). Because the amino acid sequences of the CRD in different galectins only share approximately 20%–40% homology (Oda et al, 1993), different galectins could interact with different glycoconjugated proteins, engaging different signaling pathways and yielding. Galectin-3 Negatively Regulates Memory Formation different biological effects, some overlap in binding to the same glycoconjugates is expected. Galectin-3 exists as a monomer in solution and forms pentamers upon binding to β-galactose on other proteins (Massa et al, 1993). This characteristic allows galectin-3 to function as a bridge among cells through its binding to multiple β-galactoses on different proteins. Galectin-3 is involved in pre-mRNA splicing (Dagher et al, 1995) and cell-extracellular matrix (ECM) adhesion (Kuwabara and Liu, 1996)
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
