| Rapid, concurrent alterations in pre- and postsynaptic structure induced by naturally-secreted amyloid-beta protein. | |
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MedLine Citation:
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PMID: 17368908 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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In Alzheimer's disease increasing evidence attributes synaptic and cognitive deficits to soluble oligomers of amyloid beta protein (Abeta), even prior to the accumulation of amyloid plaques, neurofibrillary tangles, and neuronal cell death. Here we show that within 1-2 h picomolar concentrations of cell-derived, soluble Abeta induce specific alterations in pre- and postsynaptic morphology and connectivity in cultured hippocampal neurons. Clusters of presynaptic vesicle markers decreased in size and number at glutamatergic but not GABAergic terminals. Dendritic spines also decreased in number and became dysmorphic, as spine heads collapsed and/or extended long protrusions. Simultaneous time-lapse imaging of axon-dendrite pairs revealed that shrinking spines sometimes became disconnected from their presynaptic varicosity. Concomitantly, miniature synaptic potentials decreased in amplitude and frequency. Spine changes were prevented by blockers of nAChRs and NMDARs. Washout of Abeta within the first day reversed these spine changes. Further, spine changes reversed spontaneously by 2 days, because neurons acutely developed resistance to continuous Abeta exposure. Thus, rapid Abeta-induced synapse destabilization may underlie transient behavioral impairments in animal models, and early cognitive deficits in Alzheimer's patients. |
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Authors:
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Barbara Calabrese; Gideon M Shaked; Iustin V Tabarean; Julia Braga; Edward H Koo; Shelley Halpain |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't Date: 2007-02-12 |
Journal Detail:
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Title: Molecular and cellular neurosciences Volume: 35 ISSN: 1044-7431 ISO Abbreviation: Mol. Cell. Neurosci. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-06-05 Completed Date: 2007-08-31 Revised Date: 2011-11-10 |
Medline Journal Info:
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Nlm Unique ID: 9100095 Medline TA: Mol Cell Neurosci Country: United States |
Other Details:
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Languages: eng Pagination: 183-93 Citation Subset: IM |
Affiliation:
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Department of Cell Biology and Institute for Childhood and Neglected Diseases, The Scripps Research Institute, 10550 North Torrey Pines Rd., La Jolla, CA 92037, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Amyloid beta-Peptides
/
immunology,
metabolism* Amyloid beta-Protein Precursor / genetics, metabolism Animals Antibodies / pharmacology Axons / drug effects, pathology*, ultrastructure Cells, Cultured Cholinergic Antagonists / pharmacology Cricetinae Cricetulus Dendrites / drug effects, pathology*, ultrastructure Excitatory Amino Acid Antagonists / pharmacology Excitatory Postsynaptic Potentials / drug effects, physiology Green Fluorescent Proteins / biosynthesis Hippocampus / cytology Mice Mutation Nerve Tissue Proteins / metabolism Neurons / cytology*, drug effects, physiology Patch-Clamp Techniques / methods Synapses / drug effects, pathology*, ultrastructure Transfection / methods |
| Grant Support | |
ID/Acronym/Agency:
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AG05131/AG/NIA NIH HHS; AG12376/AG/NIA NIH HHS; MH50861/MH/NIMH NIH HHS; NS37311/NS/NINDS NIH HHS; P50 AG005131-240037/AG/NIA NIH HHS; R01 AG012376-13/AG/NIA NIH HHS; R01 NS037311-04/NS/NINDS NIH HHS; R29 MH050861-06/MH/NIMH NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Amyloid beta-Protein Precursor; 0/Antibodies; 0/Cholinergic Antagonists; 0/Excitatory Amino Acid Antagonists; 0/Nerve Tissue Proteins; 147336-22-9/Green Fluorescent Proteins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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