Vanillin and 4-hydroxybenzyl alcohol promotes cell proliferation and neuroblast differentiation in the dentate gyrus of mice via the increase of brain-derived neurotrophic factor and tropomyosin-related kinase B

4-Hydroxy-3-methoxybenzaldehyde (vanillin) and 4-hydroxybenzyl alcohol (4-HBA) are well-known phenolic compounds, which possess various therapeutic properties and are widely found in a variety of plants. In the present study, the effects of vanillin and 4-HBA were first investigated on cell proliferation, as well as neuronal differentiation and integration of granule cells in the dentate gyrus (DG) of adolescent mice using Ki-67, doublecortin (DCX) immunohistochemistry and 5-bromo-2′-de-oxyuridine (BrdU)/feminizing Locus on X 3 (NeuN) double immunofluorescence. In both the vanillin and 4-HBA groups, the number of Ki-67(+) cells, DCX(+) neuroblasts and BrdU(+)/NeuN(+) neurons were significantly increased in the subgranular zone of the DG, as compared with the vehicle group. In addition, the levels of brain-derived neurotrophic factor (BDNF) and tropomyosin-related kinase B (TrkB), a BDNF receptor, were significantly increased in the DG in the vanillin and 4-HBA groups compared with the vehicle group. These results indicated that vanillin and 4-HBA enhanced cell proliferation, neuroblast differentiation and integration of granule cells in the DG of adolescent mice. These neurogenic effects of vanillin and 4-HBA may be closely associated with increases in BDNF and TrkB.