NMDA-receptor activation but not ion flux is required for amyloid-beta induced synaptic depression

Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (Aβ) in the etiology of Alzheimer's disease. Historically, AD research has mainly focused on the...

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Bibliographic Details
Published in:PloS one 2013-06, Vol.8 (6), p.e65350-e65350
Main Authors: Tamburri, Albert, Dudilot, Anthony, Licea, Sara, Bourgeois, Catherine, Boehm, Jannic
Format: Article
Language:English
Subjects:
Activation
Advertising executives
Alzheimer's disease
Amyloid beta-Peptides - chemistry
Amyloid beta-Peptides - pharmacology
Analysis
Animals
Biology
Brain slice preparation
Calcium
Development and progression
Etiology
Fluctuations
Glutamic Acid - metabolism
Glutamic acid receptors (ionotropic)
Hippocampus
Hippocampus - cytology
Hippocampus - drug effects
Historical account
In Vitro Techniques
Ion flux
Ion Transport
Kinases
Medicine
Memory
Metabotropic receptors
N-Methyl-D-aspartic acid receptors
Neural Inhibition - drug effects
Neurodegenerative diseases
Neuronal Plasticity - drug effects
Neurons
Peptide Fragments - chemistry
Peptide Fragments - pharmacology
Peptides
Perfusion
Phosphorylation
Protein Multimerization
Protein Structure, Secondary
Proteins
Rats
Receptor mechanisms
Receptors
Receptors, N-Methyl-D-Aspartate - metabolism
Rodents
Synapses - drug effects
Synapses - metabolism
Synaptic depression
Synaptic transmission
Synaptic Transmission - drug effects
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Description
Summary:Alzheimer disease is characterized by a gradual decrease of synaptic function and, ultimately, by neuronal loss. There is considerable evidence supporting the involvement of oligomeric amyloid-beta (Aβ) in the etiology of Alzheimer's disease. Historically, AD research has mainly focused on the long-term changes caused by Aβ rather than analyzing its immediate effects. Here we show that acute perfusion of hippocampal slice cultures with oligomeric Aβ depresses synaptic transmission within 20 minutes. This depression is dependent on synaptic stimulation and the activation of NMDA-receptors, but not on NMDA-receptor mediated ion flux. It, therefore, appears that Aβ dependent synaptic depression is mediated through a use-dependent metabotropic-like mechanism of the NMDA-receptor, but does not involve NMDA-receptor mediated synaptic transmission, i.e. it is independent of calcium flux through the NMDA-receptor.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0065350