ZFM1/SF1 mRNA in rat and gerbil brain after global ischaemia

Cerebral ischaemia results in significant brain damage, but the molecular m echanisms associated with ischaemia-induced brain injury are not well defin ed. We have adopted an improved differential-display method to search for n ew ischaemia-related genes. Among the different cDNAs isolated following tr ansient forebrain ischaemia in rat, PH3.3 was selected for further studies. The search for homologies revealed that it is the rat homologue to human z inc finger motif 1 (ZFM1), also called mammalian splicing factor 1 (SF1). W ith Northern blot, PH3.3 hybridized with three mRNA species of 2.3, 2.9 and 3.6 kb, significantly increased at 6 h and 5 days after the ischaemic insu lt. These findings were extended also to another animal model. In situ hybr idization in ischaemic gerbils showed that PH3.3 mRNA was induced in the de ntate gyrus as early as 4 h post-ischaemia. Expression peaked at 2 days in the whole hippocampus and cortex, and then progressively decreased towards sham levels. By day 4, expression had disappeared almost entirely from the cells in the CA1 region of the hippocampus, concomitant with the degenerati on of pyramidal neurons. Interestingly, ZFM1/SF1 has been recently identifi ed as activated following p53-induced apoptosis. Several lines of evidence suggest that p53 may play two roles in the post-ischaemic brain. The primar y role of p53 is to activate DNA repair processes, but if repair fails, apo ptosis will be initiated. Thus, ZFM1/SF1 may represent a relevant link betw een p53 and the neuroprotective/neurodegenerative processes which follow ce rebral ischaemia.