| DOI | Resolve DOI: https://doi.org/10.1111/j.1471-4159.2012.07783.x |
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| Author | Search for: Zeng, Y.1; Search for: Callaghan, D.1; Search for: Xiong, H.1; Search for: Yang, Z.; Search for: Huang, P.; Search for: Zhang, W.1 |
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| Affiliation | - National Research Council of Canada. NRC Institute for Biological Sciences
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| Format | Text, Article |
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| Subject | beta actin; breast cancer resistance protein; cytokine; DNA; glutathione; intercellular adhesion molecule 1; interleukin 1beta; lipid; monocyte chemotactic protein 5; transcription factor Nrf2; animal experiment; animal model; animal tissue; brain tissue; cognitive defect; developmental stage; enzyme linked immunosorbent assay; female; gel mobility shift assay; gene expression; genotype; inflammation; lipid oxidation; male; memory disorder; mouse; oxidative stress; protein deficiency; protein expression; real time polymerase chain reaction; transgenic mouse; Western blotting; Aging; Amyloid beta-Peptides; ATP-Binding Cassette Transporters; Cognition Disorders; Cytokines; Disease Progression; DNA; Encephalitis; Enzyme-Linked Immunosorbent Assay; Glutathione; Heme Oxygenase-1; Immunohistochemistry; Intercellular Adhesion Molecule-1; Maze Learning; Mice; Mice, Knockout; Mice, Transgenic; NF-E2-Related Factor 2; Oxidative Stress; Peptide Fragments; Real-Time Polymerase Chain Reaction; Signal Transduction; Mus; Mus musculus |
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| Abstract | Oxidative 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. © 2012 National Research Council Canada & The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry. |
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| Publication date | 2012 |
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| In | |
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| Language | English |
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| Peer reviewed | Yes |
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| NPARC number | 21269344 |
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| Export citation | Export as RIS |
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| Report a correction | Report a correction (opens in a new tab) |
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| Record identifier | dabadeb2-d677-402a-9cbe-a0cc2911c4bd |
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| Record created | 2013-12-12 |
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| Record modified | 2020-04-21 |
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