Wnt-5a is a synaptogenic factor with neuroprotective properties against Aβ toxicity

Lorena Varela-Nallar, Jorge Parodi, Ginny G. Farías, Nibaldo C. Inestrosa

Research output: Contribution to journalArticlepeer-review

27 Citations (Scopus)


Background: We have recently found that Wnt-5a regulates the synaptic structure and function in hippocampal neurons. This ligand is expressed in the hippocampus, stimulates dendritic spine morphogenesis and increases glutamatergic neurotransmission. Moreover, we have also shown that Wnt-5a induces the clustering of PSD-95. Objective: To explore the role of Wnt-5a in the formation of synaptic contacts. Methods: Primary rat hippocampal neurons were exposed to a formylated hexapeptide (Foxy-5) derived from the sequence of Wnt-5a to study synapse formation and function. Results: In short-term experiments, Wnt-5a only induced the clustering of PSD-95 but had no effect on the density of presynaptic puncta, while in long-term experiments, it induced both pre- and postsynaptic protein clustering and the number of synaptic contacts, in agreement with electrophysiological studies. In long-term experiments, Foxy-5 increased miniature excitatory postsynaptic current amplitude and frequency. Conclusion: Our findings indicate that Wnt-5a induces synapse formation in hippocampal neurons. In addition, we discuss recent findings indicating a neuroprotective action of Wnt-5a against Aβ neurotoxicity.

Original languageEnglish
Pages (from-to)23-26
Number of pages4
JournalNeurodegenerative Diseases
Issue number1-4
Publication statusPublished - Apr 2012


  • Alzheimer's disease
  • Miniature excitatory postsynaptic currents
  • Synaptic contacts
  • Wnt signaling pathway
  • Wnt-5a

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology


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