Journal
JOURNAL OF NEURAL TRANSMISSION
Volume 108, Issue 8-9, Pages 1065-1079Publisher
SPRINGER-VERLAG WIEN
DOI: 10.1007/s007020170025
Keywords
memory impairment; emotional behavior; beta-amyloid; cholinergic deficit; protein kinase C (PKC)
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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 3nmol/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 [H-3] 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.
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