title: Effects of streptozotocin-induced diabetes on tau phosphorylation in the rat brain.
abstract: Brain protein kinase B (Akt) and glycogen synthase kinase-3 (GSK-3) activities are adaptable to changes of peripheral blood glucose level in vivo. GSK-3 phosphorylates microtube-associated protein tau at multiple sites, which can be antagonized by protein phosphatase-2A (PP-2A). The imbalance among these enzymes might have potential connections with diabetes mellitus (DM) and Alzheimer's disease (AD). In this study hyperglycemia rat DM model was achieved by streptozotocin (STZ) treatment. The phosphorylation of tau in the rat hippocampus was detected with specific antibodies. Insulin and Li(2)CO(3) administration were also employed to find out the regulatory efforts of the kinases. We observed that rat hippocampus tau was hyperphosphorylated at Ser(396)/Ser(404) (PHF-1 sites) in STZ-induced DM model, accompanied by lowered phosphorylation levels of Akt, GSK-3 and PP-2A. Lithium, a specific GSK-3 inhibitor, nearly reversed all phosphorylation of tau at above sites in 30days. Insulin administration restored the blood glucose level in DM rats but suppressed PP-2A activity, resulting in the PHF-1 sites of tau not being dephosphorylated. These findings strongly suggest that STZ-induced hyperglycemia may cause disorder of Akt/GSK-3/PP-2A regulations in rat brain and further lead to abnormal phosphorylation of hippocampus tau.
authors.affiliation: Department of Pathophysiology, Key Laboratory of Neurological Diseases of Hubei Province, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, Hubei 430030, PR China. quzs1968@yahoo.com.cn
authors.forename: Zhongsen
authors.initials: Z
authors.lastname: Qu
authors.forename: Zongxian
authors.initials: Z
authors.lastname: Jiao
authors.forename: Xiaojiang
authors.initials: X
authors.lastname: Sun
authors.forename: Yuwu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Jinpeng
authors.initials: J
authors.lastname: Ren
authors.forename: Guogang
authors.initials: G
authors.lastname: Xu
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D016875:tau Proteins / Q000378:metabolism*
chemical_list: C489131:Mapt protein, rat; D016875:tau Proteins