DIFFERENTIAL ACTIVATION OF P38 MAPK ISOFORMS IN GLIA CELLS IN THE BRAIN FOLLOWING ISCHEMIC INSULT

초록

To study the roles of p38 MAPK isoforms in the brain of pathological condition, the expression and activity of p38a and p38b were explored in the ischemic gerbil brain. Differential activation of p38a and p38b was observed in microglia and astrocytes, respectively, after transient global ischemia. Kinase activities of both p38a and p38b were induced in hippocampus after global ischemia at different time points. The induction of p38a was proceeded and reached to the peak activation at 1-2d after ischemia, whereas the activation of p38b showed delayed and protracted induction reaching the maximum induction around 4d after ischemia. Immunological localization of p38 MAPKs in post-ischemic brain agreed with the data from kinase assay. The immunoreactivity of p38a began to be induced as early as 4 hrs after ischemic insult. The induction of p38a immunoreactivity was concentrated in the microglia in hippocampus as well as in frontal and parietal cortex of the brain, where significant neuronal damage was undergoing. It continued to increase reaching the maximum induction around 2 days after ischemic insult. In contrast, more delayed induction of p38b was observed in astrocytes in hippocampus 4 days after ischemic insult, which was remained for next several days. Interestingly, the immunoreactivities of p38a and p38b were concentrated in nucleus of microglia and astrocytes, respectively. These data suggest active and distinct roles of p38a and p38b MAPKs in post-ischemic brain.