Reversal of Synapse Degeneration by Restoring Wnt Signaling in the Adult Hippocampus

• DOI: 10.1016/j.cub.2016.07.024
• Publication Date: 2016-09-09T16:47:00Z
• Authors: Aude Marzo; Soledad Galli; Douglas Lopes; Faye McLeod; Marina Podpolny; Margarita Segovia...; Lorenza Ciani; Silvia Purro; Francesca Cacucci; Alasdair Gibb; Patricia C. Salinas
• Keywords: DKK1

Synapse degeneration occurs early in neurodegenerative diseases and correlates strongly with cognitive decline Alzheimer's disease (AD). The molecular mechanisms that trigger synapse vulnerability those promote regeneration after substantial synaptic failure remain poorly understood. Increasing evidence suggests a link between deficiency Wnt signaling AD. secreted antagonist Dickkopf-1 (Dkk1), which is elevated AD, contributes to amyloid-β-mediated failure. However, the impact of Dkk1 at circuit level mechanism by synapses disassemble have not yet been explored. Using transgenic mouse model inducibly expresses hippocampus, we demonstrate triggers loss, impairs long-term potentiation, enhances depression, induces learning memory deficits. We decipher involved loss induced as it can be prevented combined inhibition Gsk3 RhoA-Rock pathways. Notably, connectivity, reactivation pathway cessation expression completely restores number, plasticity, memory. These findings remarkable capacity adult neurons regenerate functional circuits highlight targetable for neuronal recovery degeneration.