Department of Pharmacy, College of Pharmacy, Pusan National University, Busan, 46241, Republic of Korea.
Cognitive Science Research Group, Korea Brain Research Institute, Daegu, 41062, Republic of Korea.
Arch Pharm Res. 2023 May;46(5):423-437. doi: 10.1007/s12272-023-01440-7. Epub 2023 Mar 22.
Adult neurogenesis generates new functional neurons from adult neural stem cells in various regions, including the subventricular zone (SVZ) of the lateral ventricles and subgranular zone (SGZ) of hippocampal dentate gyrus (DG). Available evidence shows hippocampal neurogenesis can be negatively or positively regulated by dietary components. In a previous study, we reported that curcumin (diferuloylmethane; a polyphenolic found in curry spice) stimulates the proliferation of embryonic neural stem cells (NSCs) by activating adaptive cellular stress responses. Here, we investigated whether subchronic administration of curcumin (once daily at 0.4, 2, or 10 mg/kg for 14 days) promotes hippocampal neurogenesis and neurocognitive function in young (5-week-old) mice. Oral administration of low-dose curcumin (0.4 mg/kg) increased the proliferation and survival of newly generated cells in hippocampus, but surprisingly, high-dose curcumin (10 mg/kg) did not effectively upregulate the proliferation or survival of newborn cells. Furthermore, hippocampal BDNF levels and phosphorylated CREB activity were elevated in only low-dose curcumin-treated mice. Passive avoidance testing revealed that low-dose curcumin increased cross-over latency times, indicating enhanced memory retention, and an in vitro study showed that low-concentration curcumin increased the proliferative activity of neural progenitor cells (NPCs) by upregulating NF1X levels. Collectively, our findings suggest that low-dose curcumin has neurogenic effects and that it may prevent age and neurodegenerative disease-related cognitive deficits.
成人神经发生是指在各种区域（包括侧脑室的室下区 [SVZ] 和海马齿状回的颗粒下区 [SGZ]）中，从成年神经干细胞产生新的功能性神经元。现有证据表明，膳食成分可以负向或正向调节海马神经发生。在之前的一项研究中，我们报道姜黄素（一种存在于咖喱香料中的多酚）通过激活适应性细胞应激反应来刺激胚胎神经干细胞（NSCs）的增殖。在这里，我们研究了亚慢性给予姜黄素（每天一次，剂量分别为 0.4、2 或 10mg/kg，持续 14 天）是否能促进年轻（5 周龄）小鼠的海马神经发生和神经认知功能。低剂量姜黄素（0.4mg/kg）的口服给药增加了海马中新生成细胞的增殖和存活，但令人惊讶的是，高剂量姜黄素（10mg/kg）并没有有效地上调新生细胞的增殖或存活。此外，仅在低剂量姜黄素处理的小鼠中，海马 BDNF 水平和磷酸化 CREB 活性升高。被动回避测试显示，低剂量姜黄素增加了交叉潜伏期时间，表明记忆保留增强，体外研究表明，低浓度姜黄素通过上调 NF1X 水平增加神经祖细胞（NPC）的增殖活性。总的来说，我们的研究结果表明，低剂量姜黄素具有神经发生作用，可能预防与年龄和神经退行性疾病相关的认知缺陷。
