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.

Abstract

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