Stimulation of zif/268 gene expression by basic fibroblast growth factor in primary rat striatal cultures

Abstract

The presence of basic fibroblast growth factor (bFGF) in the basal ganglia, and its known neurotrophic activity, has created interest in its possible role as an agent to attenuate striatal neurodegeneration. However, little information is available on the mechanisms through which bFGF might exert a long-term influence on striatal function. Primary cultures of embryonic rat striatal neurones were used to ascertain whether bFGF can alter the pattern of striatal gene expression. Treatment of cultures with bFGF (500 pM) resulted in a dramatic increase in the levels of zif/268 mRNA within 45 min. This induction was attenuated by the tyrosine kinase inhibitor genistein (100 μM), but not by its inactive structural analogue genistin (100 μM). The induction of zif/268 mRNA was found to occur in non-neuronal cells, with no increase in mRNA levels being observed in neurones. A similar induction was noted for another putative transcription factor, jun B, although no induction of the related factor jun D could be detected. These results show that bFGF can induce immediate-early gene expression in striatal cultures, and therefore that this may provide a mechanism, mediated by non-neuronal cells, which allows bFGF to cause a long-term change in striatal neurochemistry.