TRANSIENT FOREBRAIN ISCHEMIA INDUCES AN IMMEDIATE-EARLY GENE ENCODINGTHE MITOGEN-ACTIVATED PROTEIN-KINASE PHOSPHATASE 3CH134 IN THE ADULT-RAT BRAIN

In fibroblasts, ser;um stimulation has been shown to activate the imme diate-early gene 3CH134 encoding a dual specificity protein phosphatas e that regulates mitogen-activated protein kinase. We report here that 3CH134 messenger RNA levels increase during recirculation following 3 0 min forebrain ischemia in the rat brain. In normal rat brains, 3CH13 4 messenger RNA was found mainly in neurons of the cortex and thalamus . At recirculation periods up to 1 h after 30 min ischemia, 3CH134 mes senger RNA increased in neurons and glial cells of all previously isch emic brain regions. After 3 and 6 h recirculation, a prominent increas e of 3CH134 messenger RNA was observed in the pyramidal cell layer of all sectors of the hippocampus and the granule cells of the dentate gy rus, whereas in the other brain regions messenger RNA levels returned to control. Up to 6 h of recirculation the spatial induction pattern o f 3CH 134 was similar to the pattern observed for the immediate-early genes c-fos and c-jun. Within the hippocampus a similar pattern was al so observed for the heat shock protein hsp70 messenger RNA. At 12 and 24 h after ischemia, increased levels of 3CH134 messenger RNA persiste d in hippocampal neurons; at the same time a delayed increase of 3CH13 4 messenger RNA was observed in large neurons of the thalamus and in g lial cells in damaged regions of the striatum. At later survival perio ds, 3CH134 messenger RNA returned to control levels. Our study shows t hat the mitogen-activated protein kinase phosphatase 3CH134 is induced in the brain after a period of global ischemia. The expression patter n and kinetics suggest that 3CH134 is involved in the adaptive respons e of neural cells to ischemic injury, as well as in the regulation of glial cell activation.