Green tea epigallocatechin‐3‐gallate (EGCG) promotes neural progenitor cell proliferation and sonic hedgehog pathway activation during adult hippocampal neurogenesis

Adult hippocampal neurogenesis is a lifelong feature of brain plasticity that appears to be critically involved in adult brain function and neurological disease. Recent studies suggest that (-)-epigallocatechin-3-gallate (EGCG), which is the main polyphenolic constituent of green tea, may be used for the prevention and treatment of various neurodegenerative diseases. We hypothesized that EGCG promotes adult neurogenesis, which may be beneficial to hippocampus-dependent learning and memory.We show that EGCG treatment significantly increased the number of 5-bromo-2'-deoxyuridine (BrdU)-labeled cells in adult hippocampal neural progenitor cell (NPC) cultures and in the dentate gyrus of adult mice. Meanwhile, EGCG markedly improved spatial cognition in mice. These events are associated with the sonic hedgehog (Shh) signaling pathway. We observed that EGCG triggered a robust upregulation of Shh receptor (Patched) mRNA and protein expression in cultured NPCs as well as an upregulation of the downstream Shh transcriptional target Gli1. These changes were further confirmed in the hippocampus of mice administered EGCG. The blockage of the Shh signal with the pharmacological inhibitor cyclopamine attenuated EGCG-induced hippocampal neurogenesis.Our results provide strong evidence that EGCG enhances adult hippocampal neurogenesis.