title: Wnt-5a is a synaptogenic factor with neuroprotective properties against Aβ toxicity.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centro de Envejecimiento y Regeneración, Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
authors.forename: Lorena
authors.initials: L
authors.lastname: Varela-Nallar
authors.forename: Jorge
authors.initials: J
authors.lastname: Parodi
authors.forename: Ginny G
authors.initials: GG
authors.lastname: Farías
authors.forename: Nibaldo C
authors.initials: NC
authors.lastname: Inestrosa
mesh_terms: D016229:Amyloid beta-Peptides / Q000633:toxicity*; D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000166:cytology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008565:Membrane Proteins / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects* / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D051381:Rats; D013569:Synapses / Q000187:drug effects* / Q000502:physiology; D013997:Time Factors; D051153:Wnt Proteins / Q000378:metabolism*; D000071818:Wnt-5a Protein
chemical_list: D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; C542624:Foxy-5 peptide; D047908:Intracellular Signaling Peptides and Proteins; D008562:Membrane Glycoproteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D009842:Oligopeptides; C489618:Sv2a protein, rat; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; C491837:Wnt5a protein, rat