Effect of the neuroprotective compound SR57746A on nerve growth factor synthesis in cultured astrocytes from neonatal rat cortex

1 The neurotrophic factor promoting activity of the neuroprotective compoun d SR57746A was evaluated in primary cultures of neonatal rat cortical astro cytes by studying the synthesis of nerve growth factor (NGF) and brain-deri ved neurotrophic factor (BDNF). 2 A concentration- and time-dependent increase of nerve growth factor mRNA was induced by SR57746A (10 nM-1 mu M). In these astrocytes, BDNF mRNA cont ents were increased to significant but smaller extent, and beta-actin mRNA showed no variation. 3 SR57746A (1 mu M) induced increases of both de novo protein translation a fter 6 h of incubation and NGF release into the extracellular medium after 6-24 h. 4 These effects were preceded by a transient augmentation of junB, c-fos an d c-jun mRNA contents. These increases of AP-1 family mRNA were associated with increased nuclear AP-1 binding activity. 5 The results show that SR57746A can increase the synthesis and release of NGF in rat cortical astrocytes. Such effects may contribute to the drug's p reviously described neuroprotective effects.