Abstract
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.
Highlights
Neurotrophin Brain-derived neurotrophic factor (BDNF) and neurotransmitter serotonin (5-HT) regulate neuronal survival, neurogenesis, and neuronal plasticity and they co-regulate each other (Mattson et al, 2004; Martinowich and Lu, 2008)
A reduction, but not a total loss of TrkB signal was expected, since 5-HT neurons are enriched in the MB regions, they constitute a minority of all the TrkB positive cells in this region
We have investigated the role of TrkB expression in Tph2 expressing 5-HT neurons
Summary
Neurotrophin Brain-derived neurotrophic factor (BDNF) and neurotransmitter serotonin (5-HT) regulate neuronal survival, neurogenesis, and neuronal plasticity and they co-regulate each other (Mattson et al, 2004; Martinowich and Lu, 2008). Brain-derived neurotrophic factor is associated with the regulation of activity-dependent neuronal connectivity and plasticity. BDNF together with its high-affinity cognate receptor, neurotrophic tyrosine kinase receptor 2 (Ntrk2/TrkB) plays a significant role in neuronal survival, synaptic plasticity, and in mediating 5-HT metabolism (Mamounas et al, 2000). BDNF and TrkB induce serotonergic phenotype and increase the number of 5-HT expressing neurons (Galter and Unsicker, 2000a). BDNF and TrkB have been concomitantly related together with 5-HT in a myriad of neurochemical and behavioral responses (Martinowich and Lu, 2008)
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