Regulation of basic fibroblast growth factor and nerve growth factor mRNA by beta-adrenergic receptor activation and...

Basic fibroblast growth factor (bFGF) and nerve growth factor (NGF) are two neurotrophic factors that play a role in neuronal maintenance and repair. The identification and characterization of mechanisms regulating neurotrophic factor availability in the central nervous system are vital to the development of therapeutic tools for prevention of neuronal degeneration. The lipophilic beta-adrenergic receptor (BAR) agonist clenbuterol was used to assess whether activation of central BAR changes the levels of NGF and bFGF mRNA. Within 5 hr, clenbuterol (10 mg/kg, intraperitoneally) elicited a 2-3-fold increase in bFGF and NGF mRNA content in rat cerebral cortex. The induction of bFGF and NGF mRNA expression showed anatomical specificity. Among the various brain areas examined, bFGF mRNA levels were increased in the cerebral cortex, hippocampus, and cerebellum, whereas induction of NGF mRNA was observed only in the cerebral cortex. Isoproterenol, a BAR agonist that does not cross the blood-brain barrier, also elicited a 2-3-fold increase in bFGF and NGF mRNA in the cerebral cortex. Propranolol (5 mg/kg, intraperitoneally), a lipophilic BAR antagonist, blocked the induction of NGF and bFGF mRNA mediated by either isoproterenol or clenbuterol, whereas nadolol (5 mg/kg, intraperitoneally), a BAR antagonist that does not cross the blood-brain barrier, blocked only the effect of isoproterenol. Therefore, activation of both central and peripheral BAR play a role in the regulation of bFGF and NGF mRNA expression. Moreover, in adrenalectomized rats, isoproterenol failed to increase bFGF and NGF mRNA, whereas clenbuterol elicited a 2-fold increase in bFGF mRNA in the cortex and hippocampus. Our data suggest that both adrenal steroids and noradrenaline might regulate the availability of selective neurotrophic factors in the adult central nervous system.