Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg‐SwDI transgenic mice
Copyright policy )Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg‐SwDI transgenic mice
J. Neurochem. (2012) 122, 456–469.AbstractOxidative stress and neuroinflammation play important roles in Alzheimer’s disease (AD). ABCG2 is a transporter protein expressed in the brain and involved in GSH transport. To study the roles of Abcg2 in oxidative stress and AD, we cross‐bred Tg‐SwDI and Abcg2‐KO mice and generated Tg‐SwDI/Abcg2‐KO (double‐tg) mice. Brain tissues from double‐tg, Tg‐SwDI, wild‐type, and Abcg2‐KO mice at various ages were analyzed. Aβ40 and Aβ42 were detected in Tg‐SwDI and double‐tg mice. Total brain GSH was decreased and levels of lipid/DNA oxidation were increased in 3‐month double‐tg compared to Tg‐SwDI mice. Low brain GSH was still detected in 9‐month double‐tg mice. Increased HMOX‐1 and MCP‐5 expression was observed in 9‐month double‐tg mice but not in Tg‐SwDI mice compared to WT and Abcg2‐KO mice. Increased HMOX‐1 and decreased ICAM‐1 expression were observed in 12‐month double‐tg mice compared to Tg‐SwDI mice. The levels of Nrf‐2 expression and activity were decreased in 6‐month double‐tg mice. Behavioral tests show impaired cognitive/memory performance of 9‐month double‐tg compared to Tg‐SwDI mice as well as WT and Abcg2‐KO mice. These results suggest that Abcg2 deficiency increases oxidative stress and alters inflammatory response in the brain and exacerbates cognitive/memory deficit in double‐tg mice at different developmental stages.
- Southeast University China (People's Republic of)
- University of Ottawa Canada
- National Research Council Canada Canada
- National Academies of Sciences, Engineering, and Medicine United States
- Beijing Hospital China (People's Republic of)
Aging, interleukin 1beta, genotype, Western blotting, brain tissue, Mice, lipid oxidation, cognitive defect, cytokine, oxidative stress, ATP Binding Cassette Transporter, Subfamily G, Member 2, glutathione, Mice, Knockout, Mus, memory disorder, Intercellular Adhesion Molecule-1, Glutathione, Immunohistochemistry, beta actin, intercellular adhesion molecule 1, female, real time polymerase chain reaction, breast cancer resistance protein, Disease Progression, Cytokines, Encephalitis, monocyte chemotactic protein 5, Signal Transduction, NF-E2-Related Factor 2, animal experiment, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, protein deficiency, gel mobility shift assay, Real-Time Polymerase Chain Reaction, transcription factor Nrf2, animal tissue, male, lipid, Mus musculus, Animals, Maze Learning, protein expression, mouse, Amyloid beta-Peptides, animal model, DNA, Peptide Fragments, enzyme linked immunosorbent assay, transgenic mouse, developmental stage, Oxidative Stress, inflammation, gene expression, ATP-Binding Cassette Transporters, Cognition Disorders, Heme Oxygenase-1
Aging, interleukin 1beta, genotype, Western blotting, brain tissue, Mice, lipid oxidation, cognitive defect, cytokine, oxidative stress, ATP Binding Cassette Transporter, Subfamily G, Member 2, glutathione, Mice, Knockout, Mus, memory disorder, Intercellular Adhesion Molecule-1, Glutathione, Immunohistochemistry, beta actin, intercellular adhesion molecule 1, female, real time polymerase chain reaction, breast cancer resistance protein, Disease Progression, Cytokines, Encephalitis, monocyte chemotactic protein 5, Signal Transduction, NF-E2-Related Factor 2, animal experiment, Enzyme-Linked Immunosorbent Assay, Mice, Transgenic, protein deficiency, gel mobility shift assay, Real-Time Polymerase Chain Reaction, transcription factor Nrf2, animal tissue, male, lipid, Mus musculus, Animals, Maze Learning, protein expression, mouse, Amyloid beta-Peptides, animal model, DNA, Peptide Fragments, enzyme linked immunosorbent assay, transgenic mouse, developmental stage, Oxidative Stress, inflammation, gene expression, ATP-Binding Cassette Transporters, Cognition Disorders, Heme Oxygenase-1
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