RESUMO
Neurotrophin brain-derived neurotrophic factor (BDNF) and neurotransmitter serotonin (5-HT) regulate each other and have been implicated in several neuronal mechanisms, including neuroplasticity. We have investigated the effects of BDNF on serotonergic neurons by deleting BDNF receptor TrkB from serotonergic neurons in the adult brain. The transgenic mice show increased 5-HT and Tph2 levels with abnormal behavioral phenotype. In spite of increased food intake, the transgenic mice are significantly leaner than their wildtype littermates, which may be due to increased metabolic activity. Consistent with increased 5-HT, the proliferation of hippocampal progenitors is significantly increased, however, long-term survival of newborn cells is unchanged. Our data indicates that BDNF-TrkB signaling regulates the functional phenotype of 5-HT neurons with long-term behavioral consequences.
RESUMO
Neurotrophins and their receptors have highly conserved evolutionary lineage in vertebrates including zebrafish. The NTRK2 receptor has two isoforms in zebrafish, Ntrk2a and Ntrk2b. The spatio-temporal expression pattern of bdnf and ntrk2b in the zebrafish brain was studied using in situ hybridization. The robust and corresponding expression pattern of ntrk2b to bdnf suggests that ntrk2b is the key receptor for bdnf in the zebrafish brain, unlike its duplicate isoform ntrk2a. To study ntrk2b function, two different genetic strategies, the TILLING mutant and morpholino oligonucleotides (MO), were used. Specific subsets of the dopaminergic and serotonergic neuronal populations were affected in the mutants and morphants. The mutant showed anxiety- like behavior both in larval and adult stages. Our results consistently indicate that BDNF/NTRK2 signaling has a significant role in the development and maintenance of aminergic neuronal populations. Therefore, the ntrk2b-deficient zebrafish is well suited to study mechanisms relevant for psychiatric disorders attributed to a dysfunctional monoaminergic system.