Activation of Brain Wnt signaling in vivo: Effect on LTP and Neurogenesis

Abstract

The roles of the Wnt signaling pathway in several developmental processes, including synaptic differentiation, are well characterized. Wnts have a crucial role in synaptic physiology, as they modulate the synaptic vesicle cycle, the trafficking of neurotransmitter receptors and the interaction of these receptors with scaffold proteins in postsynaptic regions. Recent studies indicate that Wnts regulate synaptic plasticity and neurogenesis. We report here that the in vivo brain application of both agonists and modulators of Wnt receptors, results in improvement of several behavioral assays, concomitant with an increase in several pre and post‐synaptic proteins as well as in synaptic plasticity measured as long ‐ term potentiation (LTP) in hippocampal slices. These results were obtained with both canonical and non‐canonical Wnt modulators, including WASP‐1 and Foxy‐5. More recent studies, includes the effect of natural products as well as Wnts ligands on adult mammalian neurogenesis. In particular, we have examined the role of hypoxia on the activation of canonical Wnt signaling. Current studies are aim to ask whether non‐canonical Wnt signaling affects neurogenesis, since recent work indicated that Wnt‐5a modulates recycling of functional GABAA receptors in hippocampal neurons.