Abstract
Mice carrying mutated human APPswe and PS1 (A246E) transgenes (A/P mice) show age-dependent memory impairment in hippocampus-dependent tasks. Moreover, the mice show normal learning in the water maze within a day but impairment across days. We recorded LTP in a slice preparation (CA1) and in chronically implanted animals (dentate gyrus, or DG) at 17-18 months of age. The genotypes did not differ in the basal synaptic transmission. Also, LTP induction and its maintenance over 60 min did not differ between A/P and control mice. However, the fEPSP enhancement in vivo decayed to 77% of its maximum in 24 h in A/P mice while remaining at 96% in control mice. The time course of the LTP decay in the A/P mice corresponds to their behavioral impairment and indicates that Abeta accumulation in the dentate gyrus may interfere with the signal transduction pathways responsible for memory consolidation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Alzheimer Disease / genetics*
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Alzheimer Disease / metabolism
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Alzheimer Disease / pathology
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Amyloid beta-Peptides / toxicity*
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Amyloid beta-Protein Precursor / genetics*
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Animals
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Dentate Gyrus / growth & development
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Dentate Gyrus / metabolism
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Dentate Gyrus / pathology
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Disease Models, Animal
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Excitatory Postsynaptic Potentials / genetics
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Hippocampus / growth & development
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Hippocampus / metabolism*
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Hippocampus / pathology
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Humans
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In Vitro Techniques
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Long-Term Potentiation / genetics*
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Male
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Membrane Proteins / genetics*
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Memory Disorders / genetics*
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Memory Disorders / metabolism
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Memory Disorders / pathology
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Mice
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Mice, Transgenic
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Phenotype
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Plaque, Amyloid / genetics
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Plaque, Amyloid / metabolism
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Plaque, Amyloid / pathology
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Presenilin-1
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Synaptic Transmission / genetics
Substances
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Amyloid beta-Peptides
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Amyloid beta-Protein Precursor
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Membrane Proteins
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PSEN1 protein, human
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Presenilin-1