Wnt signaling has emerged in recent years as a major player in both nervous system development and adult synaptic plasticity. Of particular relevance to researchers studying learning and memory, Wnt signaling is critical for normal functioning of the hippocampus, a brain region that is essential for many types of memory formation and whose dysfunction is implicated in numerous neurodegenerative and psychiatric conditions. Impaired hippocampal Wnt signaling is implicated in several of these conditions, however, little is known about how Wnt signaling mediates hippocampal memory formation. This review will provide a general overview of Wnt signaling and discuss evidence demonstrating a key role for Wnt signaling in hippocampal memory formation in both normal and disease states. The regulation of Wnt signaling by ovarian sex steroid hormones will also be highlighted, given that the neuroprotection afforded by Wnt-hormone interactions may have significant implications for cognitive function in aging, neurodegenerative disease, and ischemic injury.
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