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PMID: 11466442 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Generation of aggregated beta-amyloid in the rat hippocampus impairs synaptic transmission and plasticity and causes memory deficits.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 21 ·No. 15 ·2001-08-01 ·Pages 5703-14

Stéphan A, Laroche S, Davis S

Abstract

We injected a combination of the beta-amyloids (Abetas) Abeta40 and Abeta43 to "seed" formation of amyloid deposits in the dorsal dentate gyrus of rats in vivo, on the basis of a theory of Jarrett and Landsbury (1993). Rats were tested on several different learning tasks, and synaptic transmission and plasticity were assessed in vivo. Between 7 and 16 weeks after injection, we found aggregated amyloid material, reactive astrocytosis, microgliosis, and cell loss around the sites of injection. Rats were impaired specifically in working memory type tasks in accordance with the type of memory deficit observed in the early stages of Alzheimer's disease. Synaptic transmission and long-term potentiation, a candidate cellular mechanism for memory, were severely impaired in vivo. Injections of the same dose of fragments individually did not induce these effects. These findings suggest that aggregated amyloid material induces cognitive deficits similar to those observed in the early phases of Alzheimer's disease via an alteration in neuronal transmission and plasticity.

MeSH Terms
Alzheimer Disease/etiology,physiopathology Amyloid beta-Peptides/administration & dosage,metabolism,toxicity Animals Behavior, Animal/drug effects Dentate Gyrus/drug effects,metabolism,pathology Disease Models, Animal Dose-Response Relationship, Drug Excitatory Postsynaptic Potentials/drug effects Hippocampus/drug effects,metabolism,pathology Long-Term Potentiation/drug effects Male Maze Learning/drug effects Memory Disorders/chemically induced,pathology,physiopathology Memory, Short-Term/drug effects Microinjections Neuronal Plasticity/drug effects Peptide Fragments/metabolism,toxicity Plaque, Amyloid/metabolism,pathology Rats Rats, Sprague-Dawley Rats, Wistar Synaptic Transmission/drug effects
Chemicals
Amyloid beta-Peptides Peptide Fragments amyloid beta-protein (1-40) amyloid beta-protein (1-43)
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Stéphan A
Laboratoire de Neurobiologie de l'Apprentissage, de la Mémoire et de la Communication, Centre National de la Recherche Scientifique Unité Mixte de Recherche 8620, Université Paris Sud, 91405 Orsay, France.
Laroche S
Davis S
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
Published
2001-08-01
Pages
5703-14
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6762634
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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