Diabetes synergistically exacerbates poststroke dementia and tau abnormality in brain.
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-3beta), indicating activation of GSK-3beta. 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-3beta. These findings may be helpful for developing new strategies to prevent/delay formation of poststroke dementia in patients with diabetes.
Zhang
Ting
T
Department of Neurobiology, Institute of Biomedical Sciences, State Key Laboratory of Medical Neurobiology, Shanghai Medical College, Fudan University, 138 Yi-xue-Yuan Rd., Shanghai 200032, PR China.
Pan
Bai-Shen
BS
Sun
Guang-Chun
GC
Sun
Xiao
X
Sun
Feng-Yan
FY
D000818:Animals; D015415:Biomarkers / Q000032:analysis / Q000378:metabolism; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology*; D002544:Cerebral Infarction / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D003071:Cognition / Q000502:physiology; D003704:Dementia / Q000209:etiology / Q000378:metabolism* / Q000473:pathology*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004789:Enzyme Activation / Q000187:drug effects; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D008297:Male; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020521:Stroke / Q000150:complications / Q000378:metabolism* / Q000473:pathology; D013572:Synaptic Vesicles / Q000378:metabolism / Q000473:pathology; D016875:tau Proteins / Q000378:metabolism*
D015415:Biomarkers; D016875:tau Proteins; D000071679:Glycogen Synthase Kinase 3 beta; C000605508:Gsk3b protein, rat; D038362:Glycogen Synthase Kinase 3