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1. J Neurochem. 2012 May 12. doi: 10.1111/j.1471-4159.2012.07783.x. [Epub ahead of
print]

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

Zeng Y, Callaghan D, Xiong H, Yang Z, Huang P, Zhang W.

Department of Clinical Medicine, Southeast University, Nanjing, China State Key
Laboratory of Reproductive Medicine, Dept. of Clinical Laboratory, Nanjing
Maternity and Child Healthcare Hospital Affiliated to the Nanjing Medical
University, Nanjing, China Institute for Biological Sciences, National Research
Council of Canada, Ottawa, Canada Institute of Geriatrics/Beijing Hospital,
Chinese Ministry of Health, Beijing, China Faculty of Medicine, University of
Ottawa, Ottawa, Canada.

Oxidative stress and neuroinflammation play important roles in Alzheimer's
disease (AD) (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 Journal of
Neurochemistry.

© 2012 National Research Council Canada & The Authors. Journal of Neurochemistry
© 2012 International Society for Neurochemistry Journal of Neurochemistry.

PMID: 22578166 [PubMed - as supplied by publisher]