Abstract
Galectins are a 15 member family of carbohydrate-binding proteins that have been implicated in cancer, immunity, inflammation and development. While galectins are expressed in the central nervous system, little is known about their function in the adult brain. Previously we have shown that galectin-1 (gal-1) is expressed in the adult hippocampus, and, in particular, in putative neural stem cells in the subgranular zone. To evaluate how gal-1 might contribute to hippocampal memory function here we studied galectin-1 null mutant (gal-1-/-) mice. Compared to their wildtype littermate controls, gal-1-/- mice exhibited impaired spatial learning in the water maze and contextual fear learning. Interestingly, tone fear conditioning was normal in gal-1-/- mice suggesting that loss of gal-1 might especially impact hippocampal learning and memory. Furthermore, gal-1-/- mice exhibited normal motor function, emotion and sensory processing in a battery of other behavioral tests, suggesting that non-mnemonic performance deficits are unlikely to account for the spatial and contextual learning deficits. Together, these data reveal a role for galectin-carbohydrate signalling in hippocampal memory function.
Highlights
The biological actions of carbohydrate molecules are mediated, in part, by interactions with lectins which recognize carbohydrate structures and bind to their specific sequences [1,2]
While previous cell culture studies have identified a role for gal-1 in cell death, cell adhesion and neurite outgrowth [5,6], few studies have studied the role of this lectin in central nervous system in vivo [7,8,9,10,11]
In the hippocampus we found no evidence of staining in gal-1-/- mice [9,10], suggesting that this antibody binds only gal-1, and not, for example, other members of the galectin family which exhibit structural similarity in their lectin-binding domain [5,14,15]
Summary
The biological actions of carbohydrate molecules are mediated, in part, by interactions with lectins which recognize carbohydrate structures and bind to their specific sequences [1,2]. As the hippocampus plays a central role in learning and memory, this raises the possibility that gal-1 contributes to behavioral plasticity either via neurogenic or non-neurogenic (as gal-1 is expressed in mature neurons in the CA1 and CA3 regions of the hippocampus) mechanisms. To evaluate this possibility here we characterize gal-1-/- mice in a range of learning and memory tasks, and we find that hippocampus-dependent contextual and spatial learning is deficient in these mice. These experiments reveal an important role for gal-1 in hippocampus-dependent learning and memory, and, more generally, represent a first step toward understanding how lectin-carbohydrate signalling contributes to hippocampal memory function
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