Department of Medical Genetics, Third Military Medical University, Chongqing, P. R. China.
Mol Nutr Food Res. 2012 Aug;56(8):1292-303. doi: 10.1002/mnfr.201200035. Epub 2012 Jun 13.
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.
成人海马神经发生是大脑可塑性的终身特征，似乎对成年大脑功能和神经疾病有至关重要的影响。最近的研究表明，(-)-表没食子儿茶素没食子酸酯（EGCG），作为绿茶的主要多酚成分，可用于预防和治疗各种神经退行性疾病。我们假设 EGCG 能促进成年神经发生，这可能对海马依赖的学习和记忆有益。
我们发现 EGCG 处理显著增加了成年海马神经祖细胞（NPC）培养物和成年小鼠齿状回中 5-溴-2'-脱氧尿苷（BrdU）标记细胞的数量。同时，EGCG 显著改善了小鼠的空间认知能力。这些事件与 sonic hedgehog（Shh）信号通路有关。我们观察到 EGCG 在培养的 NPC 中触发了 Shh 受体（ patched）mRNA 和蛋白表达的强烈上调，以及下游 Shh 转录靶标 Gli1 的上调。这些变化在给予 EGCG 的小鼠海马体中得到了进一步证实。用药理学抑制剂环巴胺阻断 Shh 信号会减弱 EGCG 诱导的海马神经发生。
我们的结果提供了强有力的证据，表明 EGCG 增强了成年海马神经发生。
