| Summary: | <p>Abstract</p> <p>Background</p> <p>Soluble amyloid-β (Aβ;) oligomers have been recognized to be early and key intermediates in Alzheimer's disease (AD)-related synaptic dysfunction. Aβ oligomers block hippocampal long-term potentiation (LTP) and impair rodent spatial memory. <it>Wnt </it>signaling plays an important role in neural development, including synaptic differentiation.</p> <p>Results</p> <p>We report here that the <it>Wnt </it>signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that <it>Wnt-5a </it>increases the amplitude of field excitatory postsynaptic potentials (fEPSP) and both AMPA and NMDA components of the excitatory postsynaptic currents (EPSCs), without modifying the paired pulse facilitation (PPF). Conversely, in the presence of Aβ oligomers the fEPSP and EPSCs amplitude decreased without modification of the PPF, while the postsynaptic scaffold protein (PSD-95) decreased as well. Co-perfusion of hippocampal slices with <it>Wnt-5a </it>and Aβ oligomers occludes against the synaptic depression of EPSCs as well as the reduction of PSD-95 clusters induced by Aβ oligomers in neuronal cultures. Taken together these results indicate that <it>Wnt-5a </it>and Aβ oligomers inversely modulate postsynaptic components.</p> <p>Conclusion</p> <p>These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical <it>Wnt </it>pathway activation.</p>
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