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Hypoxia-induced tau phosphorylation and memory deficit in rats.
- Source :
-
Neuro-degenerative diseases [Neurodegener Dis] 2014; Vol. 14 (3), pp. 107-16. Date of Electronic Publication: 2014 Jun 27. - Publication Year :
- 2014
-
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.<br /> (© 2014 S. Karger AG, Basel.)
- Subjects :
- Alzheimer Disease
Animals
Glycogen Synthase Kinase 3 metabolism
Glycogen Synthase Kinase 3 beta
Hypoxia complications
Male
Malondialdehyde metabolism
Maze Learning physiology
Memory Disorders etiology
Methylation
Oxidative Stress physiology
Phosphorylation
Protein Phosphatase 2 genetics
Protein Phosphatase 2 metabolism
Rats, Sprague-Dawley
Spatial Memory physiology
Superoxide Dismutase metabolism
tau Proteins genetics
Hippocampus physiopathology
Hypoxia physiopathology
Memory Disorders physiopathology
tau Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1660-2862
- Volume :
- 14
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Neuro-degenerative diseases
- Publication Type :
- Academic Journal
- Accession number :
- 24993525
- Full Text :
- https://doi.org/10.1159/000362239