[Mechanism of tau hyperphosphorylation in brain cortex of diabetic rats and effect of LiCl].
OBJECTIVE
To explore the mechanism of tau hyperphosphorylation and the effect of LiCl on tau phosphorylation and the memory retention deficits in streptozotocin-induced diabetes mellitus (DM) rats.


METHODS
The rats were randomly divided into control, DM, DM + NaCl, and DM + LiCl groups and diabetes was induced by streptozotocin. The activity of glycogen synthase kinase-3 (GSK-3) was measured by 32P-labelling. The level of tau phosphorylated and changes of memory retention were examined by Western blotting and step down test, respectively.


RESULTS
Compared with control group, the activity of GSK-3 and tau phosphorylation was increased, and the memory retention was impaired in DM group. When the rats were treated with LiCl, the activity of GSK-3 and hyperphosphorylation of tau were significantly arrested (P < 0.05, P < 0.01), and the memory retention deficit was significantly improved (P < 0.05).


CONCLUSIONS
The hyperphosphorylation of tau can be induced by activation of GSK-3 in diabetic rats. Lithium protects tau from hyperphosphorylation and may rescue memory retention in the rats by inhibiting GSK-3 activity.
Qu
Zhong-sen
ZS
Department of Pathophysiology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China.
Tian
Qing
Q
Zhou
Xin-wen
XW
Wang
Qun
Q
Zhang
Qi
Q
Wang
Jian-zhi
JZ
D000818:Animals; D002540:Cerebral Cortex / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism; D018021:Lithium Chloride / Q000627:therapeutic use*; D008297:Male; D008569:Memory Disorders / Q000188:drug therapy* / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
D016875:tau Proteins; D038362:Glycogen Synthase Kinase 3; D018021:Lithium Chloride