Premium
P2‐064: HO‐1/STEROL‐OXYSTEROL INTERACTIONS IN ALZHEIMER'S DISEASE: A SYNTHESIS
Author(s) -
Hascalovici Jacob Reuben,
Schipper Hyman
Publication year - 2014
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2014.05.738
Subject(s) - oxysterol , neurodegeneration , sterol , heme oxygenase , homeostasis , biology , biliverdin reductase , heme , genetically modified mouse , microbiology and biotechnology , sterol regulatory element binding protein , cholesterol , biliverdin , transgene , neuroscience , biochemistry , medicine , disease , enzyme , gene
Background:Alzheimer’s disease (AD) can be understood in the context of ageing because much evidence has implicated oxidative stress (increase of oxidants and decrease of antioxidants) in the pathogenesis and etiology of AD. Previous studies show premature neuroimmunoendocrine aging in a triple-transgenic mouse model for AD (3xTg-AD). Although the contribution to AD of the oxidative stress present in the brain is accepted, the peripheral oxidative redox state has scarcely been studied. Therefore, in the present work the changes in the redox state of several peripheral tissues at early stages of the disease have been studied in 3xTgAD mice. Methods: Male and female young (4 months-old) and adult (6-9 month-old) 3xTgAD and non-transgenic (NTgAD) mice were used. In the liver, spleen, thymus, kidney, heart and lung of these animals, several oxidants and antioxidants such as xanthine oxidase (XO) activity, the total glutathione (GSH) levels, the total antioxidant capacity (T-AOC), as well as the activities of glutathione peroxidase (GPx) and reductase (GR) were analysed. Results: In general, both young and adult male and female 3xTgAD mice, compared with NTgAD animals, showed a decrease in antioxidant defences (GSH, GPx, and GR) and an increase in XO activity in most tissues studied. Nevertheless, these differences were higher in young than in adult mice in the case of the spleen. Furthermore, the differences between 3xTgAD and NTgAD are more exacerbated in male than in female mice, the 3xTgAD males showing a significant decrease in antioxidant defenses and an increased XO activity with respect to the females, especially at 4 and 6 months of age. Conclusions: These results show that 3xTgAD young and adult mice suffer a high oxidative stress at peripheral levels, which has already appeared at 4 months of age. Moreover, 3xTgAD male mice have a worse oxidative redox state than females, especially at 4 and 6 month of age. Thus, 3xTgAD mice suffer premature ageing, which is underpinned by an oxidative stress state, and could explain their early mortality. The analysis of the peripheral oxidative stress, which could be detected at early stages of the disease, seems to be a good marker of the progression of AD.