Dynamic expression of TrkB receptor protein on proliferating and maturing cells in the adult mouse dentate gyrus

Abstract

Brain-derived neurotrophic factor (BDNF) is implicated in the regulation of adult hippocampal neurogenesis, presumably via its primary receptor, TrkB. However, controversy exists about how BDNF affects neurogenesis (e.g., proliferation vs. survival/differentiation). This controversy arises, in part, due to the lack of information about whether and when TrkB is expressed on adult neural precursors in vivo. We utilized multiple methods to analyze proliferating and maturing cells in the adult mouse subgranular zone (SGZ) for TrkB protein. Using bromodeoxyuridine (BrdU) to "birthdate" cells, we found that the proportion of proliferating cells that were TrkB-immunoreactive (IR) was low and remained low for at least 1 week, but increased with further survival after BrdU labeling. Use of the nestin-GFP transgenic mouse and the immature neuron marker, doublecortin (Dcx), revealed that the likelihood of being TrkB-IR increased with presumed maturity of the cell type. Stem-like cells, which rarely divide, were likely to express TrkB protein. However, early progenitors (GFP+/Dcx-) and late progenitors (GFP+/Dcx+), both of which are still in the cell cycle, were unlikely to be TrkB-IR. Immature neuroblasts (GFP-/Dcx+) were more likely to express TrkB, especially as they presented a more mature morphology. Taken together, these findings emphasize that expression of TrkB protein is closely linked to progression toward neuronal maturity. This provides evidence that maturing, but not proliferating, cells in the adult mouse SGZ have the molecular machinery necessary to respond directly to BDNF. Furthermore, these findings lay critical groundwork for further exploration of the role of BDNF-TrkB signaling in regulation of adult hippocampal neurogenesis.