title: Memory impairment induced by chronic intracerebroventricular infusion of beta-amyloid (1-40) involves downregulation of protein kinase C.
abstract: Signaling pathways underlying the cognitive deficit of the Alzheimer's disease (AD) are not completely understood. Protein kinase C (PKC), a major neuronal protein plays a critical role in cellular signal transduction and it is known to be subjected to modulation in AD. We showed previously that, chronic infusion of beta-amyloid (1-40) into rat cerebroventricle leads to deficit in spatial and non-spatial memory formation. As an attempt to identify the cellular correlates of the memory deficit, in the present study we investigated the PKC activation in different brain areas. Chronic infusion of beta-amyloid (1-40) for 14 days into the rat cerebroventricle decreased the activity of soluble protein kinase C (PKC) in the hippocampus. Subcellular translocation of PKC to membrane fraction in hippocampal slices of rats treated with beta-amyloid (1-40) was completely abolished under acute stimulation with 0.5 microM phorbol-dibutyrate (PDBu). We also reported a decreased affinity (k(D)) for PDBu binding in the hippocampus, cerebral cortex and striatum. The total number of binding sites for PDBu (B(max)) was increased, in the three brain areas analyzed on the day 14, but the changes were not statistically significant. Our data indicate that chronic accumulation of beta-amyloid (1-40) into the rat brain reduced activation of PKC, effect that would substantially contribute to the memory deficit found in these animals.
authors.affiliation: Department of Neuropsychopharmacology and Hospital Pharmacy, Nagoya University Graduate School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya, Japan.
authors.forename: Ana
authors.initials: A
authors.lastname: Olariu
authors.forename: Kiyofumi
authors.initials: K
authors.lastname: Yamada
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Mamiya
authors.forename: Vasile
authors.initials: V
authors.lastname: Hefco
authors.forename: Toshitaka
authors.initials: T
authors.lastname: Nabeshima
mesh_terms: D000544:Alzheimer Disease / Q000201:enzymology* / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism* / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites / Q000187:drug effects / Q000502:physiology; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D002908:Chronic Disease; D004195:Disease Models, Animal; D015536:Down-Regulation / Q000187:drug effects / Q000502:physiology*; D006624:Hippocampus / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D007276:Injections, Intraventricular; D008297:Male; D008569:Memory Disorders / Q000139:chemically induced / Q000201:enzymology* / Q000503:physiopathology; D017072:Neostriatum / Q000187:drug effects / Q000201:enzymology / Q000503:physiopathology; D010446:Peptide Fragments / Q000378:metabolism* / Q000494:pharmacology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000378:metabolism*; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions
chemical_list: D016229:Amyloid beta-Peptides; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); D015240:Phorbol 12,13-Dibutyrate; D011493:Protein Kinase C