title: Abcg2 deficiency augments oxidative stress and cognitive deficits in Tg-SwDI transgenic mice.
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.
authors.affiliation: Department of Clinical Medicine, Southeast University, Nanjing, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zeng
authors.forename: Debbie
authors.initials: D
authors.lastname: Callaghan
authors.forename: Huaqi
authors.initials: H
authors.lastname: Xiong
authors.forename: Ze
authors.initials: Z
authors.lastname: Yang
authors.forename: Peilin
authors.initials: P
authors.lastname: Huang
authors.forename: Wandong
authors.initials: W
authors.lastname: Zhang
mesh_terms: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters / Q000172:deficiency* / Q000235:genetics*; D000375:Aging / Q000235:genetics / Q000523:psychology; D016229:Amyloid beta-Peptides / Q000032:analysis / Q000172:deficiency / Q000235:genetics / Q000378:metabolism; D000818:Animals; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology*; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D018450:Disease Progression; D004660:Encephalitis / Q000235:genetics / Q000473:pathology; D004797:Enzyme-Linked Immunosorbent Assay; D005978:Glutathione / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D051267:NF-E2-Related Factor 2 / Q000502:physiology; D018384:Oxidative Stress / Q000235:genetics*; D010446:Peptide Fragments / Q000032:analysis / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology
chemical_list: D000070997:ATP Binding Cassette Transporter, Subfamily G, Member 2; D018528:ATP-Binding Cassette Transporters; C501412:Abcg2 protein, mouse; D016229:Amyloid beta-Peptides; D016207:Cytokines; C090509:Icam1 protein, mouse; D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D010446:Peptide Fragments; C078592:amyloid beta-protein (1-40); C075222:amyloid beta-protein (1-42); D018799:Intercellular Adhesion Molecule-1; D004247:DNA; D051547:Heme Oxygenase-1; D005978:Glutathione