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J Neurosci. 2014 Feb 5;34(6):2191-202. doi: 10.1523/JNEUROSCI.0862-13.2014.

In vivo activation of Wnt signaling pathway enhances cognitive function of adult mice and reverses cognitive deficits in an Alzheimer's disease model.

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Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8331150, Chile, and Centro de Neurobiología y Plasticidad Cerebral, Departamento de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, Valparaíso 2360102, Chile.


The role of the Wnt signaling pathway during synaptic development has been well established. In the adult brain, different components of Wnt signaling are expressed, but little is known about its role in mature synapses. Emerging in vitro studies have implicated Wnt signaling in synaptic plasticity. Furthermore, activation of Wnt signaling has shown to protect against amyloid-β-induced synaptic impairment. The present study provides the first evidence that in vivo activation of Wnt signaling improves episodic memory, increases excitatory synaptic transmission, and enhances long-term potentiation in adult wild-type mice. Moreover, the activation of Wnt signaling also rescues memory loss and improves synaptic dysfunction in APP/PS1-transgenic mice that model the amyloid pathology of Alzheimer's diseases. These findings indicate that Wnt signaling modulates cognitive function in the adult brain and could be a novel promising target for Alzheimer's disease therapy.


APP/PS1 mice; Alzheimer's disease; Wnt signaling; cognitive function; memory; synaptic plasticity

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