FoxO3a Changes in Pyramidal Neurons and Expresses in Non-Pyramidal Neurons and Astrocytes in the Gerbil Hippocampal CA1 Region After Transient Cerebral Ischemia

The forkhead box O (FoxO) proteins regulate processes ranging from cell longevity to cell apoptosis and function as transcription factors. FoxO3a is expressed throughout the brain including the hippocampus. In the present study, we investigated the changes in FoxO3a immunoreactivity and its protein levels in the gerbil hippocampal CA1 region after 5 min of transient global cerebral ischemia. FoxO3a immunoreactivity and protein levels in the ischemic CA1 region, which is very vulnerable to ischemic damage, were slightly decreased from 3 h after ischemia-reperfusion (I-R) and maintained until 12 h after I-R. One and 2 days after I-R, FoxO3a immunoreactivity and protein levels were similar to those in the sham-operated group. At 3 days after I-R, FoxO3a immunoreactivity and protein levels were markedly increased in the CA1 region. FoxO3a immunoreactivity was hardly detected in pyramidal neurons from 5 days after I-R; however, at 5 days after I-R, FoxO3a immunoreactivity was detected in astrocytes and GABAergic interneurons of the ischemic CA1 region. These results indicate that both FoxO3a immunoreactivity and protein levels are distinctively altered in the ischemic CA1 region after transient cerebral ischemia, and that the changes in FoxO3a expression may be related to the ischemia-induced delayed neuronal death.