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Molecular Neurodegeneration

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Open Access 01-12-2010 | Research article

Wnt-5aoccludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons

Authors: Waldo Cerpa, Ginny G Farías, Juan A Godoy, Marco Fuenzalida, Christian Bonansco, Nibaldo C Inestrosa

Published in: Molecular Neurodegeneration | Issue 1/2010

Abstract

Background

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. Wnt signaling plays an important role in neural development, including synaptic differentiation.

Results

We report here that the Wnt signaling activation prevents the synaptic damage triggered by Aβ oligomers. Electrophysiological analysis of Schaffer collaterals-CA1 glutamatergic synaptic transmission in hippocampal slices indicates that Wnt-5a 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 Wnt-5a 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 Wnt-5a and Aβ oligomers inversely modulate postsynaptic components.

Conclusion

These results indicate that post-synaptic damage induced by Aβ oligomers in hippocampal neurons is prevented by non-canonical Wnt pathway activation.

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Title: Wnt-5aoccludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons
Authors: Waldo Cerpa
Ginny G Farías
Juan A Godoy
Marco Fuenzalida
Christian Bonansco
Nibaldo C Inestrosa
Publication date: 01-12-2010
Publisher: BioMed Central
Published in: Molecular Neurodegeneration / Issue 1/2010
Electronic ISSN: 1750-1326
DOI: https://doi.org/10.1186/1750-1326-5-3

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Wnt-5aoccludes Aβ oligomer-induced depression of glutamatergic transmission in hippocampal neurons

Abstract

Background

Results

Conclusion

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Results

Conclusion

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