OPPOSITE REGULATION OF BASIC FIBROBLAST GROWTH-FACTOR AND NERVE GROWTH-FACTOR GENE-EXPRESSION IN RAT CORTICAL ASTROCYTES FOLLOWING DEXAMETHASONE TREATMENT

Growth factors are peptides that exert different activities in the CNS , supporting the survival of different cell populations and playing an important role in the maintenance of cell homeostasis. Much evidence has suggested that these molecules can protect neurons from degenerati on induced by mechanical injury or excitotoxic stimuli. Different fact ors can contribute to the regulation of neurotrophic factor expression in the brain. Such mechanisms may therefore be important in the manip ulation of the levels of these peptides in specific brain areas as a t herapeutic intervention in acute and chronic neurodegenerative disease s. We have used a primary culture of rat cortical astrocytes to invest igate the regulation of basic fibroblast growth factor (bFGF) gene exp ression in comparison with other neurotrophic molecules. Our results i ndicate that the glucocorticoid analogue dexamethasone markedly elevat es bFGF mRNA levels but reduces the expression of nerve growth factor. The induction of bFGF was transient, as it peaked after 6 h and retur ned to basal levels within 24 h and was not blocked by coincubation of cycloheximide, thus indicating that it did not require de novo protei n synthesis. This effect was also observed in vivo, as systemic inject ion of dexamethasone (1 or 10 mg/kg) produced a significant increase i n the amount of bFGF mRNA in cerebral cortex and hippocampus. The effe ct we describe can contribute to the regulation of bFGF expression in the brain and may be important in relation to the protective effect ex erted by this growth factor in different models of neuronal injury.