AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss

Hsieh, H., Boehm, J., Sato, C., Iwatsubo, T., Tomita, T., Sisodia, S., Malinow, R. (December 2006) AMPAR removal underlies Abeta-induced synaptic depression and dendritic spine loss. Neuron, 52 (5). pp. 831-43. ISSN 0896-6273 (Print)

URL: https://www.ncbi.nlm.nih.gov/pubmed/17145504
DOI: 10.1016/j.neuron.2006.10.035

Abstract

Beta amyloid (Abeta), a peptide generated from the amyloid precursor protein (APP) by neurons, is widely believed to underlie the pathophysiology of Alzheimer's disease. Recent studies indicate that this peptide can drive loss of surface AMPA and NMDA type glutamate receptors. We now show that Abeta employs signaling pathways of long-term depression (LTD) to drive endocytosis of synaptic AMPA receptors. Synaptic removal of AMPA receptors is necessary and sufficient to produce loss of dendritic spines and synaptic NMDA responses. Our studies indicate the central role played by AMPA receptor trafficking in Abeta-induced modification of synaptic structure and function.

Item Type: Paper
Uncontrolled Keywords: Alphavirus Infections genetics Amyloid beta-Protein physiology Animals Cells Cultured DNA/biosynthesis genetics Dendritic Spines drug effects physiology ultrastructure Electrophysiology Endocytosis genetics physiology Enzyme-Linked Immunosorbent Assay Excitatory Amino Acid Antagonists pharmacology Excitatory Postsynaptic Potentials drug effects Image Processing Computer-Assisted Immunoblotting Mutation/physiology Neuronal Plasticity drug effects physiology Neurons physiology ultrastructure Patch-Clamp Techniques Phosphorylation Rats Receptors AMPA drug effects genetics physiology Receptors Metabotropic Glutamate biosynthesis genetics Sindbis Virus genetics Synapses drug effects/*physiology ultrastructure Transfection p38 Mitogen-Activated Protein Kinases genetics physiology
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > dendritic cells

diseases & disorders > mental disorders > mood disorders > depression
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > glutamate receptor
CSHL Authors:
Communities: CSHL labs > Malinow lab
Depositing User: CSHL Librarian
Date: 7 December 2006
Date Deposited: 14 Dec 2011 14:39
Last Modified: 18 Apr 2018 18:59
PMCID: PMC1850952
Related URLs:
URI: http://repository.cshl.edu/id/eprint/22821

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