Oxidative damage increased in presenilin1/presenilin2 conditional double knockout mice.
- Author:
Dong-Li ZHANG
1
;
Yi-Qun CHEN
;
Xu JIANG
;
Ting-Ting JI
;
Bing MEI
Author Information
- Publication Type:Journal Article
- MeSH: Age Factors; Alzheimer Disease; genetics; metabolism; physiopathology; Amyloid beta-Peptides; urine; Animals; Deoxyguanosine; analogs & derivatives; urine; Disease Models, Animal; Enzyme-Linked Immunosorbent Assay; methods; Glutathione; metabolism; Hydrazines; metabolism; Lipid Peroxidation; genetics; Malondialdehyde; metabolism; Mice; Mice, Inbred CBA; Mice, Knockout; physiology; Oxidation-Reduction; Oxidative Stress; physiology; Peptide Fragments; urine; Presenilin-1; deficiency; Presenilin-2; deficiency; Spectrophotometry, Atomic; methods; Superoxide Dismutase; metabolism
- From:Neuroscience Bulletin 2009;25(3):131-137
- CountryChina
- Language:English
-
Abstract:
OBJECTIVEThis report aims to describe the oxidative damage profile in brain of presenilin1 and presenilin2 conditional double knockout mice (dKO) at both early and late age stages, and to discuss the correlation between oxidative stress and the Alzheimer-like phenotypes of dKO mice.
METHODSThe protein level of Abeta(42) in dKO cortex and free 8-OHdG level in urine were measured by ELISA. Thiobarbituric acid method and spectrophotometric DNPH assay were used to determine the lipid peroxidation and protein oxidation in cortex, respectively. SOD and GSH-PX activities were assessed by SOD Assay Kit-WST and GSH-PX assay kit, separately.
RESULTSSignificant decrease of Abeta(42) was verified in dKO cortex at 6 months as compared to control mice. Although lipid peroxidation (assessed by MDA) was increased only in dKO cortex at 3 months and protein oxidation (assessed by carbonyl groups) was basically unchanged in dKO cortex, ELISA analysis revealed that free 8-OHdG, which was an indicator of DNA lesion, was significantly decreased in urine of dKO mice from 3 months to 12 months. Activities of SOD and GSH-PX in dKO and control cortices showed no statistical difference except a significant increase of GSH-PX activity in dKO mice at 9 months.
CONCLUSIONOxidative damage, especially DNA lesion, was correlated with the neurodegenerative symptoms that appeared in dKO mice without the deposition of Abeta(42). Triggers of oxidative damage could be the inflammatory mediators released by activated microglia and astrocytes.
