title: Alterations in behavior, amyloid beta-42, caspase-3, and Cox-2 in mutant PS2 transgenic mouse model of Alzheimer's disease.
abstract: Alzheimer's disease (AD) occurs when neurons in the memory and cognition regions of the brain are accompanied by an accumulation of the long amyloid beta-proteins of the 39 to 43 amino acids derived from the amyloid precursor protein (APP) by cleavage with beta- and gamma-secretase. An increased production of Abeta-42 by mutation of PS2 genes promotes caspase expression and is associated with the Cox-2 found in the brain of AD patients. To address this question in vivo, we expressed the human mutant PS2 (hPS2m) (N141I) as well as wild PS2 (hPS2w) as a control in transgenic (Tg) mice under control of the neuron-specific enolase (NSE) promoter. Water maze tests were used to demonstrate the behavioral defect; dot blot, Western blot, and immunohistochemical analyses were performed on the brain with the hPS2, Abeta-42, caspase-3, and Cox-2 antibody. We concluded that 1) Tg mice showed a behavioral dysfunction in the water maze test, 2) levels of hPS2, Abeta-42, caspase-3, and Cox-2 expression were modulated in the brains of both Tg mice, 3) dense staining with antibody to hPS2, Abeta-42, caspase-3, and Cox-2 was visible in the brains of Tg mice compared with age-matched control mice, and 4) distinguishable AD phenotypes between hPS2w- and hPS2m-Tg mice did not appear. These results suggest that an elevation of Abeta-42 by overexpression of hPS2 and mutation of hPS2m might induce the behavioral deficit and caspase-3 and Cox-2 induction, which could be useful in the therapeutic testing of compounds to have considerable clinical effects.
authors.affiliation: Division of Laboratory Animal Resources, Korea FDA, National Institute of Toxicological Research, Seoul 122-704, Korea.
authors.forename: Dae Y
authors.initials: DY
authors.lastname: Hwang
authors.forename: Kab R
authors.initials: KR
authors.lastname: Chae
authors.forename: Tae S
authors.initials: TS
authors.lastname: Kang
authors.forename: Jin H
authors.initials: JH
authors.lastname: Hwang
authors.forename: Chae H
authors.initials: CH
authors.lastname: Lim
authors.forename: Hyun K
authors.initials: HK
authors.lastname: Kang
authors.forename: Jun S
authors.initials: JS
authors.lastname: Goo
authors.forename: Mi R
authors.initials: MR
authors.lastname: Lee
authors.forename: Hwa J
authors.initials: HJ
authors.lastname: Lim
authors.forename: Sae H
authors.initials: SH
authors.lastname: Min
authors.forename: Jun Y
authors.initials: JY
authors.lastname: Cho
authors.forename: Jin T
authors.initials: JT
authors.lastname: Hong
authors.forename: Chi W
authors.initials: CW
authors.lastname: Song
authors.forename: Sang G
authors.initials: SG
authors.lastname: Paik
authors.forename: Jung S
authors.initials: JS
authors.lastname: Cho
authors.forename: Yong K
authors.initials: YK
authors.lastname: Kim
mesh_terms: D000544:Alzheimer Disease / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism*; D051546:Cyclooxygenase 2; D004195:Disease Models, Animal; D015870:Gene Expression; D005838:Genotype; D006801:Humans; D007150:Immunohistochemistry; D007527:Isoenzymes / Q000378:metabolism*; D018782:Maze Learning / Q000502:physiology; D008565:Membrane Proteins / Q000235:genetics* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009154:Mutation; D010446:Peptide Fragments / Q000378:metabolism*; D010751:Phosphopyruvate Hydratase / Q000235:genetics; D053766:Presenilin-2; D011401:Promoter Regions, Genetic / Q000235:genetics; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D007527:Isoenzymes; D008565:Membrane Proteins; C508861:PSEN2 protein, human; D010446:Peptide Fragments; D053766:Presenilin-2; D011993:Recombinant Fusion Proteins; C075222:amyloid beta-protein (1-42); D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; C505407:CASP3 protein, human; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020169:Caspases; D010751:Phosphopyruvate Hydratase