Beta-amyloid oligomers affect the structure and function of the postsynaptic region: role of the Wnt signaling pathway.
BACKGROUND
Alzheimer's disease (AD) is the most prevalent neurodegenerative disease in the growing population of elderly people. Synaptic dysfunction is an early manifestation of AD. The cellular mechanism by which beta-amyloid peptide (Abeta) affects synapses remains unclear. Abeta oligomers target synapses in cultured rat hippocampal neurons suggesting that they play a key role in the regulation of synapses.


OBJECTIVE
The aim of this work is to study the effect of Abeta oligomers on the central synapses and the possible role of the Wnt signaling pathway in preventing the Abeta effects.


METHODS
We used rat hippocampal neurons, immunofluorescence and western blot procedures to detect synaptic proteins.


RESULTS
Abeta oligomers induced a reduction of the postsynaptic density protein 95 (PSD-95) and the NMDA glutamate receptors. We found that Wnt-5a, a noncanonical Wnt ligand, prevents the decrease triggered by Abeta oligomers in the glutamate receptor and PSD-95.


CONCLUSIONS
Altogether, our results suggest that Abeta oligomers decrease the synaptic responses by affecting the postsynaptic region at different levels. The Wnt signaling activation prevents synaptic damage induced by Abeta, which raises the possibility of a new therapeutic intervention for the treatment of synaptic changes observed in AD.
Dinamarca
Margarita C
MC
Centro de Regulación Celular y Patología Joaquín V. Luco, MIFAB, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago, Chile.
Colombres
Marcela
M
Cerpa
Waldo
W
Bonansco
Christian
C
Inestrosa
Nibaldo C
NC
D016229:Amyloid beta-Peptides / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D000076122:Disks Large Homolog 4 Protein; D006624:Hippocampus / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D008565:Membrane Proteins / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D009474:Neurons / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction / Q000502:physiology*; D013329:Structure-Activity Relationship; D013569:Synapses / Q000737:chemistry / Q000473:pathology* / Q000502:physiology; D051153:Wnt Proteins / Q000502:physiology*
D016229:Amyloid beta-Peptides; D000076122:Disks Large Homolog 4 Protein; C501449:Dlg4 protein, rat; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D016194:Receptors, N-Methyl-D-Aspartate; D051153:Wnt Proteins