SPERMIDINE SPERMINE N-1-ACETYLTRANSFERASE MESSENGER-RNA LEVELS SHOW MARKED AND REGION-SPECIFIC CHANGES IN THE EARLY PHASE AFTER TRANSIENT FOREBRAIN ISCHEMIA/

Considerable evidence points to an involvement of natural polyamines ( putrescine, spermidine and spermine) in trophic regulation of brain ti ssue. Spermidine/spermine N-1-acetyltransferase is the key enzyme in t he interconversion pathway which leads to the formation of spermidine and putrescine from spermine and spermidine, respectively. In the pres ent paper we have studied using in situ hybridization histochemistry t he levels of spermidine/spermine N-1-acetyltransferase mRNA in the rat central nervous system after transient forebrain ischemia. In the fir st hours after the insult, a modest increase in spermidine/spermine N- 1-acetyltransferase mRNA levels was observed in ependymal cells and ot her non-neuronal cells of all telencephalic and diencephalic regions. In addition, major increases in spermidine/spermine N-1-acetyltransfer ase mRNA levels were observed in regions selectively vulnerable to the ischemic insult, such as striatum, hippocampus and cerebral cortex, d uring the first day post-reperfusion. The time course and extent of la belling increase were subregion- and cell-specific. At the cellular le vel, the labelling appeared markedly increased in neurons (8-10 fold i n ventromedial striatum and CA1 region) and, to a lesser extent, in no n-neuronal cells. The increase in SSAT mRNA levels was not directly re lated to cell degeneration, as it was detected in both some vulnerable and some resistant cell populations. However, the peak increase of SS AT labelling was precocious in resistant neurons (such as those of ven tromedial striatum and dentate gyrus granular layer) and delayed or ve ry limited in vulnerable neurons (such as those of CA1 pyramidal layer and dorsolateral striatum). The increase in spermidine/spermine N-1-a cetyltransferase may contribute to the increase in putrescine and decr ease in spermidine levels observed after ischemia and gives further su pport to the notion that polyamine metabolism in the early phase after lesion is oriented towards putrescine production. This phenomenon cou ld be relevant in determining the prevalence of neurotrophic vs. neuro toxic effects of polyamines.