Grape seed extract enhances neurogenesis in the hippocampal dentate gyrus in C57BL/6 mice

The effects of grape seed extract (GSE), a major source of phenolic compounds, were examined on cell proliferation, neuroblast differentiation and integration into granule cells in the hippocampal dentate gyrus (DG) of middle-aged (12 month-old) mice using Ki67, doublecortin (DCX) immunohistochemistry and 5'-bromo-2-deoxyguanosine (BrdU)/calbindin D-28k (CB) double immunofluorescence study, respectively. GSE (25, 50 and 100 mg/kg) was administered orally for 28 days, and the animals were treated with 50 mg/kg BrdU intraperitoneally on the day of first GSE treatment. In the vehicle-treated group, Ki67 and DCX immunoreactivity was detected in the subgranular zone of the DG (SZDG). GSE treatment dose-dependently increased the number of Ki67 and DCX immunoreactive cells, particularly the number of DCX immunoreactive neuroblasts with well-developed (tertiary) dendrites. GSE also dose-dependently increased DCX protein levels. In addition, GSE treatment increased significantly the number of BrdU/CB double labeled granule cells. These results suggest that GSE significantly increases cell proliferation, neuroblast differentiation and integration into granule cells in the DG, and the consumption of GSE enhances the plasticity of hippocampus in middle-aged mice.