Lack of serotonin in the rat brain alters BDNF expression during adulthood

It is well established that alterations of the serotoninergic system may contribute to the pathophysiology of mood disorders. Using Zinc-finger nuclease technology we recently generated rats deficient in TPH2, the enzyme responsible for serotonin synthesis in the brain. We took advantage of this animal model, lacking serotonin in the brain, to investigate whether a vulnerable genotype can be associated with alterations of neuronal plasticity, which appear to be relevant for psychopathological risk. More specifically, we analyzed the expression of the neurotrophin Brain-Derived Neurotrophic Factor (BDNF) because of its important role in adult neuronal plasticity and its association with mood disorders. The BDNF system is very complex both at transcriptional and translational levels. The Bdnf gene consists of nine 5’ untranslated exons, each linked to individual promoter regions, and a 3’ coding exon (IX), which codes for the BDNF protein. The transcription of each untranslated exon is driven by a separate promoter controlled by an array of signaling mechanisms. We found that total Bdnf mRNA levels were significantly increased in the prefrontal cortex as well as in the ventral hippocampus of Tph2-deficient male rats, whereas in the dorsal hippocampus we observed a significant increase of the long 3’UTR Bdnf transcript levels. Interestingly these changes were due to a significant upregulation of specific Bdnf isoforms. In summary changes in Bdnf expression observed in Tph2-deficient rats can be relevant for behavioural abnormalities associated with the lack of serotonin in the brain