Focal cerebral ischemia induces Alzheimer's disease-like pathological change in rats.
The changes in the tau protein phosphorylation and expression of bcl-2, and bax in rat parietal cortex neurons after focal cerebral ischemia-reperfusion (I/R) were explored, and the relationship between the tau protein phosphorylation and the expression of bax or apoptosis was clarified in order to elucidate the relationship between cerebral infarction and Alzheimer's disease. The rat focal cerebral I/R model was induced by occlusion of the right middle cerebral artery using the intraluminal suture method. The level of tau protein phosphorylation at Ser396, Ser404, Tyr231, Ser199/202 sites and the expression of bcl-2, bax and total tau 5 in rat parietal cortex during focal cerebral ischemia/reperfusion were detected by Western blot. The relationship between the tau protein phosphorylation and the expression of bax, or apoptosis was examined by TUNEL method and double-labeling immunofluorenscence method. The results showed that the level of tau hyperphosphorylation at Ser199 / 202, Ser396, Ser404, Tyr231 sites and the expression levels of bcl-2, and bax were significantly higher in I/R group than in the sham group, but the ratio of bcl-2/bax was decreased. Neuronal apoptosis, bax expression and the tau protein hyperphosphorylation were co-localized. It is suggested that Alzheimer's disease-like pathological changes occur after cerebral I/R. The highly abnormal phosphorylation of tau protein plays a key role in cerebral I/R-induced apoptosis. The cerebral infarction may contribute to Alzheimer's disease occurrence and development.
Department of Neurosurgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. wwanghhaijjun@sina.com
Haijun
H
Wang
Hongyang
H
Zhao
Youfan
Y
Ye
Nanxiang
N
Xiong
Junhong
J
Huang
Dongxiao
D
Yao
Yin
Y
Shen
Xintong
X
Zhao
D000544:Alzheimer Disease / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D002545:Brain Ischemia / Q000473:pathology*; D008297:Male; D009474:Neurons / Q000473:pathology; D010296:Parietal Lobe / Q000473:pathology; D010766:Phosphorylation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000473:pathology*; D051028:bcl-2-Associated X Protein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism*
C494828:Bax protein, rat; D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D016875:tau Proteins