Abstract
In the present study we found that chronic infusion of beta-amyloid fragment (25-35) at nanomolar concentration into rat cerebral ventricle impairs learning and memory. At a concentration of 3 nmol/day but not 0.3 nmol/day, beta-amyloid significantly reduced the spontaneous alternation behavior and the memory performance in the water maze and multiple passive avoidance tests. A significant increase in anxiety was also found in the animals infused with 3 nmol/day beta-amyloid fragment. Memory deficits and the increased emotionality were correlated with a decreased nicotine-evoked acetylcholine release from the frontal cortex/hippocampus, as assessed by microdialysis, in freely moving rats. The amyloid fragment infused either at pico- or nanomolar concentrations reduced the affinity of [3H] phorbol dibutyrate binding, an index of activated protein kinase C (PKC), and increased the total number of binding sites in the hippocampal particulate fraction. Our results suggest that the amnesic and anxiogenic effects of chronic infusion of beta-amyloid (25-35) are related to the decreased acetylcholine release and reduced PKC activation.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Acetylcholine / metabolism*
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Affective Symptoms / chemically induced
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Affective Symptoms / enzymology*
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Affective Symptoms / physiopathology
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Alzheimer Disease / enzymology*
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Alzheimer Disease / physiopathology
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Amyloid beta-Peptides / metabolism
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Amyloid beta-Peptides / pharmacology*
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Animals
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Anxiety / chemically induced
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Anxiety / enzymology
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Anxiety / physiopathology
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Avoidance Learning / drug effects
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Avoidance Learning / physiology
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Binding Sites / drug effects
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Binding Sites / physiology
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Binding, Competitive / drug effects
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Binding, Competitive / physiology
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Cell Membrane / drug effects
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Cell Membrane / metabolism
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Dose-Response Relationship, Drug
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Drug Administration Schedule
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Hippocampus / drug effects*
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Hippocampus / enzymology
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Hippocampus / physiopathology
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Male
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Maze Learning / drug effects
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Maze Learning / physiology
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Memory Disorders / chemically induced
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Memory Disorders / enzymology*
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Memory Disorders / physiopathology
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Motor Activity / drug effects
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Motor Activity / physiology
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Peptide Fragments / metabolism
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Peptide Fragments / pharmacology*
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Protein Kinase C / drug effects*
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Protein Kinase C / metabolism
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Rats
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Rats, Wistar
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Tritium / pharmacokinetics
Substances
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Amyloid beta-Peptides
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Peptide Fragments
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amyloid beta-protein (25-35)
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Tritium
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Protein Kinase C
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Acetylcholine