https://www.abbs.info
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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]