P4–028: Tau release from hTau mouse primary neuronal cultures

reperfusion. Here we observe whether inhibition of GSK-3 b improves spatial learning and memory performance and tau hyper phosphorylation after cerebral ischemia-reperfusion in rats. Methods: The 3-month-old male Sprague-dawley rats were grouped sham group, cerebral ischemia-reperfusion (I/R) group and a group of cerebral ischemia-reperfusion followed by injection of SB216763 (SB) into coccygeal vein, which is a special inhibitor of GSK-3 b. Rats of I/R group were subjected to middle cerebral artery occlusion for1 hour and followed by reperfusion for 48 hours. Rats of the injection group were followed by reperfusion and injected SB into tail vein once a day after cerebral ischemia for 1 hour. Spatial learning and memory of rats were detected by the Morris water maze and the levels of tau phosphorylation were detected by western blotting and immunohistochemistry in the brain. Results: Compared with I/R group, rats in the injection group have significantly short escape latency of acquisition phase during training and test in the Morris water maze. We detected cAMP responsive element binding protein (CREB) level. It showed that the levels of CREB increased and the levels of ser142 phosphorylation of CREB decreased in hippocampus and cortex of rats injected SB, compared with rats of I/R group. Levels of tau phosphorylation at ser396, ser404 and thr231 increased observably in hippocampus and cortex of rats after cerebral ischemia-reperfusion, and decreased significantly after injection of SB. Conclusions: Inhibition of GSK-3 b can improve AD-like impairment induced by cerebral ischemiareperfusion. GSK-3 b may be an important therapeutic target for cerebral ischemia-reperfusion injury.