http://www.abbs.info      E-mail: [email protected]

ISSN 1672-9145                                                Acta Biochim Biophys Sin 2004, 36(12): 803–810                                                  CN 31-1940/Q

Correlation of Behavior Changes and BOLD Signal in Alzheimer-like Rat Model

Zheng-Hui HU#, Xiao-Chuan WANG1#, Li-Yun LI3, Mai-Li LIU3, Rong LIU1, Zhiqun LING1, Qing TIAN1, Xiao-Wei TANG, Yi-Gen WU2*, and Jian-Zhi WANG1*

 

Department of Physics and Bio-X disciplinary Laboratory, Zhejiang University, Hangzhou 310027,China;

1Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China;

2Institute of High Energy Physics and Key Laboratory of Nuclear Analysis Techniques, Chinese Academy of Sciences, P.O. Box 918, Beijing 100039, China;

3Wuhan Institute of Physics and Mathematics, State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics,

Chinese Academy of Sciences, Wuhan 430071, China

 

Abstract        To explore a potential means for the early diagnosis of Alzheimer disease, we studied the relationship of resting T2* signal and tau hyperphosphorylation/spatial memory deficit. The rat model with tau hyperphosphorylation and spatial memory deficit was established by bilateral hippocampi injection of isoproterenol (IP). Then, the correlative alteration between resting T2* signal and spatial memory retention was assessed with blood oxygenation level dependent (BOLD) functional magnetic resonance imaging (fMRI) study and Morris Water Maze test, and Western blot was employed to confirm tau hyperphosphorylation. The analysis showed following results. (1) Tau phosphorylation at Ser396/Ser404 and Ser199/Ser202 was significantly increased in IP-injected rats as detected by PHF-1 and tau-1, respectively. (2) An AD-like spatial memory retention disturbance was induced at 24 h after isoproterenol injection. (3) A sensitivity threshold of resting T2* signal intensity, which separated the IP-treated rats from vehicle control, was obtained by applying linear regression analysis, and an estimated sensitivity statistical threshold was at 32.62. These results suggest that resting T2* signal may serve as a noninvasive quantitative marker in predicting AD-like spatial memory deficits and tau hyperphosphorylation.

 

Key words        Alzheimer disease (AD); functional magnetic resonance imaging (fMRI); isoproterenol (IP); Morris Water Maze; diagnosis

 

 

-----------------

Received: August 25, 2004        Accepted: October 25, 2004

This work was supported by the grants from the Natural Science Foundation of China (No. 39925012, No. 30100057, and No. 30170221), the Major State Basic Research Development Program of China (G1999054007, G19990504006) and National Educational Committee of China (2001-171)

#These authors contributed equally to this work

*Corresponding authors:

Jian-Zhi WANG: Tel, 86-27-83692625; Fax, 86-27-83693883; E-mail, [email protected]

Yi-Gen WU: Tel, 86-10-88233185; Fax, 86-10-88233186; E-mail, [email protected]