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.

ABSTRACT

4-Hydroxy­3-methoxybenzaldehyde (vanillin) and 4-hydroxybenzyl alcohol (4-HBA) are well­known 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 4­HBA 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 Ki­67, doublecortin (DCX) immunohistochemistry and 5­bromo­2'­deoxyuridine (BrdU)/feminizing Locus on X 3 (NeuN) double immunofluorescence. In both the vanillin and 4­HBA groups, the number of Ki­67+ 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 brain­derived neurotrophic factor (BDNF) and tropomyosin­related kinase B (TrkB), a BDNF receptor, were significantly increased in the DG in the vanillin and 4­HBA groups compared with the vehicle group. These results indicated that vanillin and 4­HBA enhanced cell proliferation, neuroblast differentiation and integration of granule cells in the DG of adolescent mice . These neurogenic effects of vanillin and 4­HBA may be closely associated with increases in BDNF and TrkB.