EFFECTS OF ATP ANALOGS AND BASIC FIBROBLAST GROWTH-FACTOR ON ASTROGLIAL CELL-DIFFERENTIATION IN PRIMARY CULTURES OF RAT STRIATUM

We have used primary cultures of rat striatum to study the effects of ATP analogues on the elongation of astrocytic processes, a parameter o f astroglial cell differentiation. Parallel studies were performed wit h basic fibroblast growth factor, a known regulator of astroglial cell function. After three days in culture, both the growth factor and alp ha beta-methylene-ATP induced dramatic increases in the mean length of astrocytic processes/cell. For both agents, effects were dose-depende nt. The effect of alpha beta-methylene-ATP was antagonized by the tryp anoside suramin and mimicked by 2-methyl-thio-ATP, suggesting the invo lvement of a suramin-sensitive P2-purinoceptor. Neither all additive n or a synergistic effect between ap-methylene-ATP and basic fibroblast growth factor on the elongation of processes was detected in cultures exposed to both agents. Indeed, an inhibition with respect to the effe cts induced by either agent alone was recorded, suggesting that the gr owth factor and the purine analogue can modulate astrocytic differenti ation by activation of common intracellular pathways. It is concluded that, like basic fibroblast growth factor, ATP can promote the maturat ion of astrocytes towards a more differentiated phenotype characterize d by the presence of longer astrocytic processes. These findings might have interesting implications for astroglial cell differentiation dur ing brain development and for ischemia- and trauma-associated hypergli osis.