BDNF INDUCTION OF TRYPTOPHAN-HYDROXYLASE MESSENGER-RNA LEVELS IN THE RAT-BRAIN

We have previously demonstrated an augmentation of serotonergic activi ty within various brain areas following infusion of brain-derived neur otrophic factor (BDNF) into the midbrain near the periaqueductal gray and dorsal and median raphe nuclei (PAG/DR), However, the mechanism of this BDNF-induced modulatory effect on serotonergic systems was uncle ar, The aim of the present work was to study the regulation of tryptop han hydroxylase (TPH) mRNA levels after chronic BDNF administration in vivo, TPH mRNA levels were measured using a quantitative competitive reverse transcription polymerase chain reaction (RT-PCR) assay. A sign ificant increase in the expression of TPH mRNA (13-fold) was found wit hin the PAG/DR as early as 24 hr after onset of BDNF infusion and was sustained throughout the duration of infusion (11 days), This was acco mpanied by increased serotonin (5-hydroxytryptamine, 5-HT) levels and decreased nociceptive responsiveness assessed by tail-flick latency. B DNF induction of TPH mRNA levels was also observed in a serotonergic c ell line derived from raphe neurons, indicating that BDNF can directly regulate TPH mRNA levels. These results suggest that BDNF augments 5- HT synthesis in vivo by directly enhancing steady-state TPH mRNA level s, and subsequently leading to marked behavioral alterations. (C) 1998 Wiley-Liss, Inc.