期刊
NEUROCHEMISTRY INTERNATIONAL
卷 56, 期 8, 页码 955-961出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuint.2010.04.003
关键词
Stroke; Dementia; Tau phosphorylation; Diabetes; GSK-3 beta; beta-Amyloid; Cerebral ischemia; Alzheimer's disease
资金
- NBRP of China [2006CB504100, 2006943702]
- NSF of China [30770660, J0730860]
- SMF [07D214005]
This study investigated whether exacerbation of poststroke dementia by diabetes associated abnormal tau phosphorylation and its mechanism. Streptozotocin (STZ) injection and/or a high fat diet (HFD) were used to treat rats to induce type 1 and 2 diabetes. Animals were randomly divided into STZ, HFD, STZ-HFD, and normal diet (NPD) groups. Focal ischemic stroke was induced by middle cerebral artery occlusion (MCAO). Cognitive function was tested by the Morris water maze. STZ or STZ-HFD treatment exacerbated ischemia-induced cognitive deficits, brain infarction and reduction of synaptophysin expression. Moreover, we found that diabetes further increased AT8, a marker of hyperphosphorylated tau, protein and immunopositive stained cells in the hippocampus of rats following MCAO while reduced the level of phosphorylated glycogen synthase kinase 3-beta at serine-9 residues (p-ser9-GSK-3 beta), indicating activation of GSK-3 beta. We conclude that diabetes further deteriorates ischemia-induced brain damage and cognitive deficits which may be associated with abnormal phosphorylation of tau as well as activation of GSK-3 beta. These findings may be helpful for developing new strategies to prevent/delay formation of poststroke dementia in patients with diabetes. (C) 2010 Elsevier Ltd. All rights reserved.
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