Different expression of glycogen synthase kinase-3beta between young and old rat brains after transient middle cerebral artery occlusion.

Ischemia is a common stress to human brain and is difficult to cure in older individuals. To examine the differences of the response to cerebral ischemia between young and old rat brains, distributions of glycogen synthase kinase-3beta (GSK3beta) and tau proteins were analyzed after 90 min of transient middle cerebral artery occlusion (MCAO) in young (10-11 weeks) and old (15 months) rats by immunohistochemical analyses. At 4 h of reperfusion, strong cytoplasmic and nuclear immunoreactivity for GSK3beta was induced in neurons of lamina I, II, V and VI of the cerebral cortex and dorsal caudate in young brains, while the induction was not observed in lamina I and II of old cerebral cortex. The staining in lamina V and VI and dorsal caudate then gradually decreased until seven days of reperfusion in both animal groups. The staining of tau protein and terminal deoxynucleotidyl transferase-mediated dUTP-biotin in situ nick end labeling (TUNEL) did not show any positive signals in the control brain, but showed positive signals after ischemia with a peak at 24 h and 3 days, respectively. No significant difference was observed in the temporal and spatial patterns of tau and TUNEL stainings between these two groups. These data suggest that GSK3beta may have a role in ischemic neuronal cell death, and that the different spatial expression of GSK3beta between young and old rat brains may partly explain the vulnerability of older neurons after ischemia.