Amyloid beta from axons and dendrites reduces local spine number and plasticity

Wei, W., Nguyen, L. N., Kessels, H. W., Hagiwara, H., Sisodia, S., Malinow, R. (2010) Amyloid beta from axons and dendrites reduces local spine number and plasticity. Nature Neuroscience, 13 (2). 190-U71. ISSN 1097-6256

URL: http://www.ncbi.nlm.nih.gov/pubmed/20037574
DOI: 10.1038/nn.2476

Abstract

Excessive synaptic loss is thought to be one of the earliest events in Alzheimer's disease. Amyloid beta (A beta), a peptide secreted in an activity-modulated manner by neurons, has been implicated in the pathogenesis of Alzheimer's disease by removing dendritic spines, sites of excitatory synaptic transmission. However, issues regarding the subcellular source of A beta, as well as the mechanisms of its production and actions that lead to synaptic loss, remain poorly understood. In rat organotypic slices, we found that acute overproduction of either axonal or dendritic A beta reduced spine density and plasticity at nearby (similar to 5-10 mu m) dendrites. The production of A beta and its effects on spines were sensitive to blockade of action potentials or nicotinic receptors; the effects of A beta (but not its production) were sensitive to NMDA receptor blockade. Notably, only 30-60 min blockade of A beta overproduction permitted induction of plasticity. Our results indicate that continuous overproduction of A beta at dendrites or axons acts locally to reduce the number and plasticity of synapses.

Item Type: Paper
Uncontrolled Keywords: LONG-TERM POTENTIATION NICOTINIC ACETYLCHOLINE-RECEPTORS PROTEIN TRANSGENIC MICE ALZHEIMERS-DISEASE A-BETA SYNAPTIC PLASTICITY PRECURSOR PROTEIN IN-VIVO HIPPOCAMPAL-NEURONS RAT HIPPOCAMPUS
Subjects: diseases & disorders > mental disorders > delirium dementia cognitive disorders > Alzheimer's disease
organism description > animal > mammal > rodent > mouse
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons
organs, tissues, organelles, cell types and functions > cell types and functions > cell types > neurons

organism description > animal > mammal > rodent > rat
organism description > animal > mammal > rodent > rat

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > transgenic animal
CSHL Authors:
Communities: CSHL labs > Malinow lab
Watson School > Publications
Depositing User: CSHL Librarian
Date Deposited: 20 Oct 2011 14:08
Last Modified: 22 Sep 2014 19:33
PMCID: PMC3310198
Related URLs:
URI: http://repository.cshl.edu/id/eprint/15582

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