title: Hypoxia-induced tau phosphorylation and memory deficit in rats.
abstract: Hypoxia was shown to be associated with an increased risk of Alzheimer's disease (AD). The effects of hypoxia on the development of AD pathology and spatial memory ability and the possible molecular mechanisms remain poorly understood. In this study, we demonstrate that rats exposed to a hypoxic condition (10% oxygen concentration) for 1, 2, 4 and 8 weeks (6 h each day) displayed spatial memory impairment and increased tau phosphorylation at Ser198/199/202, Thr205, Ser262, Ser396 and Ser404 in the hippocampus. Concomitantly, the levels of Tyr216-phosphorylated glycogen synthase kinase (GSK)-3β (activated form of GSK-3β) and Tyr307-phosphorylated protein phosphatase 2A (inactivated form of PP2A) were significantly increased in the hippocampus of the rats with 1, 2, 4 and 8 weeks of hypoxia exposure, while the levels of methylated PP2A (activated form of PP2A) were significantly decreased in the hippocampus of the rats with 4 and 8 weeks of hypoxia exposure. In addition, the content of malondialdehyde, an indicator of oxidative stress, was elevated, whereas the activity of superoxide dismutase was not significantly changed in the hippocampus of the rats exposed to hypoxia. Taken together, these data demonstrated that hypoxia induced tau hyperphosphorylation and memory impairment in rats, and that the increased tau phosphorylation could be attributed to activation of GSK-3β and inactivation of PP2A. These data suggest that interventions to improve hypoxia may be helpful to prevent the development of AD pathology and cognitive impairment.
authors.affiliation: Department of Pathophysiology, Guangzhou Medical University, Guangzhou, China.
authors.forename: Chang-E
authors.initials: CE
authors.lastname: Zhang
authors.forename: Xifei
authors.initials: X
authors.lastname: Yang
authors.forename: Lingyun
authors.initials: L
authors.lastname: Li
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Sui
authors.forename: Qing
authors.initials: Q
authors.lastname: Tian
authors.forename: Wei
authors.initials: W
authors.lastname: Wei
authors.forename: Jianzhi
authors.initials: J
authors.lastname: Wang
authors.forename: Gongping
authors.initials: G
authors.lastname: Liu
mesh_terms: D000544:Alzheimer Disease; D000818:Animals; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D006624:Hippocampus / Q000503:physiopathology*; D000860:Hypoxia / Q000150:complications / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000378:metabolism; D018782:Maze Learning / Q000502:physiology; D008569:Memory Disorders / Q000209:etiology / Q000503:physiopathology*; D008745:Methylation; D018384:Oxidative Stress / Q000502:physiology; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000235:genetics / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D065852:Spatial Memory / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: C489131:Mapt protein, rat; D016875:tau Proteins; D008315:Malondialdehyde; D013482:Superoxide Dismutase; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3; D054648:Protein Phosphatase 2