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

A. Olariu, M. H. Tran, K. Yamada, M. Mizuno, V. Hefco, T. Nabeshima

Research output: Contribution to journalArticle

Abstract

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 3nmol/day but not 0.3nmol/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 3nmol/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.

Original languageEnglish
Pages (from-to)1065-1079
Number of pages15
JournalJournal of Neurology
Volume248
Issue number9
Publication statusPublished - 12-09-2001
Externally publishedYes

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All Science Journal Classification (ASJC) codes

  • Neurology
  • Clinical Neurology

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