Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg-SwDI transgenic mice

  1. Get@NRC: Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg-SwDI transgenic mice (Opens in a new window)
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Journal titleJournal of Neurochemistry
Pages456469; # of pages: 14
Subjectbeta 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; article; brain tissue; cognitive defect; controlled study; developmental stage; enzyme linked immunosorbent assay; female; gel mobility shift assay; gene expression; genotype; inflammation; lipid oxidation; male; memory disorder; mouse; nonhuman; oxidative stress; priority journal; protein deficiency; protein expression; real time polymerase chain reaction; transgenic mouse; Western blotting; Aging; Amyloid beta-Peptides; Animals; 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
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. © 2012 National Research Council Canada & The Authors. Journal of Neurochemistry © 2012 International Society for Neurochemistry.
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AffiliationNational Research Council Canada (NRC-CNRC); NRC Institute for Biological Sciences (IBS-ISB)
Peer reviewedYes
NPARC number21269344
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Record identifierdabadeb2-d677-402a-9cbe-a0cc2911c4bd
Record created2013-12-12
Record modified2016-05-09
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