Memory deficits and increased emotionality induced by beta-amyloid (25-35) are correlated with the reduced acetylcholine release and altered phorbol dibutyrate binding in the hippocampus.
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.
Olariu
A
A
Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, Japan.
Tran
M H
MH
Yamada
K
K
Mizuno
M
M
Hefco
V
V
Nabeshima
T
T
D000109:Acetylcholine / Q000378:metabolism*; D000342:Affective Symptoms / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001007:Anxiety / Q000139:chemically induced / Q000201:enzymology / Q000503:physiopathology; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001667:Binding, Competitive / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D006624:Hippocampus / Q000187:drug effects* / Q000201:enzymology / Q000503:physiopathology; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008569:Memory Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D009043:Motor Activity / Q000187:drug effects / Q000502:physiology; D010446:Peptide Fragments / Q000378:metabolism / Q000494:pharmacology*; D011493:Protein Kinase C / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014316:Tritium / Q000493:pharmacokinetics
D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C074636:amyloid beta-protein (25-35); D014316:Tritium; D011493:Protein Kinase C; D000109:Acetylcholine