Alterations in behavior, amyloid p‐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.

Overexpression of human selenoprotein M differentially regulates the concentrations of antioxidants and H2O2, the activity of antioxidant enzymes, and the composition of white blood cells in a transgenic rat

“…Immunohistochemical analysis was performed as previously described (11,12). Briefly, the level Figure 1.…”

Modulators of amyloid protein aggregation and toxicity: EGCG and CLR01

“…Mice treated with EGCG through either administration route also showed improved performance in the radial arm water maze [113], a task of working memory. In a different study, one week of oral 3 mg/kg EGCG treatment of mice expressing a presenilin 2 mutation (Asn141→Ile) [114] showed decreased levels of Aβ42, measured by ELISA, compared to vehicle-treated mice [115].…”

Acquisition of conditioned taste aversion is impaired in the amyloid precursor protein/presenilin 1 mouse model of Alzheimer’s disease

“…Mice expressing mutations in amyloid precursor protein (APP), presenilin-1 (PS1), presenilin-2 (PS2), tau or apolipoprotein (apoE) have been generated to model various behavioral physiological, pathological and biochemical aspects of AD (Corder et al, 1998, Ashe, 2000, Lewis et al, 2001, Gordon et al, 2002, Hwang et al, 2002, Jolas et al, 2002, Teter et al, 2002. The mice developed thus far to investigate the pathology and learning and memory associated deficits in AD do not include a mouse that possesses all of the 1 Correspondence: Dr. Paul J. Pistell, Nutritional Neuroscience and Aging Laboratory, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, Louisiana 70808, Tel: 225/763-2739, Fax: 225/763-0261, Email:Paul.Pistell@pbrc.edu Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication.…”