Summary.
In the present study we found that chronic infusion of β-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, β-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 β-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 β-amyloid (25–35) are related to the decreased acetylcholine release and reduced PKC activation.
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Received February 14, 2001; accepted March 13, 2001
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Olariu, A., Tran, M., Yamada, K. et al. Memory deficits and increased emotionality induced by β-amyloid (25–35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus. J Neural Transm 108, 1065–1079 (2001). https://doi.org/10.1007/s007020170025
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DOI: https://doi.org/10.1007/s007020170025