Transient Cerebral Ischemia Alters GSK-3β and p-GSK-3β Immunoreactivity in Pyramidal Neurons and Induces p-GSK-3β Expression in Astrocytes in the Gerbil Hippocampal CA1 Area

Glycogen synthase kinase 3 beta (GSK-3 beta) is a key downstream protein in the PI3K/Akt pathway. Phosphorylation of serine 9 of GSK-3 beta (GSK-3 beta activity inhibition) promotes cell survival. In this study, we examined changes in expressions of GSK-3 beta and phosphorylation of GSK-3 beta (p-GSK-3 beta) in the gerbil hippocampal CA1 area after 5 min of transient cerebral ischemia. GSK-3 beta immunoreactivity in the CA1 area was increased in pyramidal cells at 6 h after ischemia-reperfusion. It was decreased in CA1 pyramidal cells from 12 h after ischemia-reperfusion, and hardly detected in the CA1 pyramidal cells at 5 days after ischemia-reperfusion. p-GSK-3 beta immunoreactivity was slightly decreased in CA1 pyramidal cells at 6 and 12 h after ischemia-reperfusion. It was significantly increased in these cells at 1 and 2 days after ischemia-reperfusion. Five days after ischemia-reperfusion, p-GSK-3 beta immunoreactivity was hardly found in CA1 pyramidal cells. However, p-GSK-3 beta immunoreactivity was strongly expressed in astrocytes primarily distributed in strata oriens and radiatum. In conclusion, GSK-3 beta and p-GSK-3 beta were significantly changed in pyramidal cells and/or astrocytes in the gerbil hippocampal CA1 area following 5 min of transient cerebral ischemia. This finding indicates that GSK-3 beta and p-GSK-3 beta are closely related to delayed neuronal death.