Ortiz-López L, Márquez-Valadez B, Gómez-Sánchez A, Silva-Lucero M D C, Torres-Pérez M, Téllez-Ballesteros R I, Ichwan M, Meraz-Ríos M A, Kempermann G, Ramírez-Rodríguez G B
Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico.
Laboratory of Neurogenesis, Division of Clinical Investigations, National Institute of Psychiatry "Ramón de la Fuente Muñiz", Calz. México-Xochimilco 101, 14370 México D.F., Mexico; Program of Master in Biological Sciences of UNAM, México, D.F., Mexico.
Neuroscience. 2016 May 13;322:208-20. doi: 10.1016/j.neuroscience.2016.02.040. Epub 2016 Feb 23.
Epigallo-catechin-3-gallate (EGCG), found in the leaves of Camellia sinensis (green tea), has antioxidant- and scavenger-functions and acts neuroprotectively. It has been publicized as anti-aging remedy but data on potential cellular mechanisms are scarce. Recent studies claimed that EGCG specifically promotes neural precursor cell proliferation in the dentate gyrus of C57Bl/6 mice, without changes at the level of immature and mature new neurons. We here analyzed the effects of EGCG on adult hippocampal neurogenesis in male Balb/C mice and saw a different pattern. Two weeks of treatment with EGCG (0, 0.625, 1.25, 2.5, 5 and 10mg/kg) showed a dose-response curve that peaked at 2.5mg/kg of EGCG with significantly increased cell survival without affecting cell proliferation but decreasing apoptotic cells. Also, EGCG increased the population of doublecortin-(DCX)-expressing cells that comprises the late intermediate progenitor cells (type-2b and -3) as well as immature neurons. After EGCG treatment, the young DCX-positive neurons showed more elaborated dendritic trees. EGCG also significantly increased net neurogenesis in the adult hippocampus and increased the hippocampal levels of phospho-Akt. Ex vivo, EGCG exerted a direct effect on survival and neuronal differentiation of adult hippocampal precursor cells, which was absent, when PI3K, a protein upstream of Akt, was blocked. Our results thus support a pro-survival and a pro-neurogenic role of EGCG. In the context of the conflicting published results, however, potential genetic modifiers must be assumed. These might help to explain the overall variability of study results with EGCG. Our data do indicate, however, that natural compounds such as EGCG can in principle modulate brain plasticity.
表没食子儿茶素-3-没食子酸酯（EGCG）存在于茶树（绿茶）叶片中，具有抗氧化和清除自由基的功能，并发挥神经保护作用。它已被宣传为抗衰老疗法，但关于潜在细胞细胞机制的细胞机制的数据却很少。最近的研究表明，EGCG能特异性促进C57Bl/6小鼠齿状回中神经前体细胞的增殖，而未成熟和成熟新神经元水平没有变化。我们在此分析了EGCG对雄性Balb/C小鼠成年海马神经发生的影响，发现了不同的模式。用EGCG（0、0.625、1.25、2.5、5和10mg/kg）处理两周显示出剂量反应曲线，在2.5mg/kg的EGCG时达到峰值，细胞存活率显著增加，不影响细胞增殖，但减少凋亡细胞。此外，EGCG增加了双皮质素（DCX）表达细胞的数量，这些细胞包括晚期中间祖细胞（2b型和3型）以及未成熟神经元。EGCG处理后，年轻的DCX阳性神经元显示出更复杂的树突。EGCG还显著增加了成年海马中的净神经发生，并提高了海马中磷酸化Akt的水平。在体外，EGCG对成年海马前体细胞的存活和神经元分化有直接影响，而当Akt上游的一种蛋白质PI3K被阻断时，这种影响就不存在了。因此，我们的结果支持EGCG具有促存活和促神经发生的作用。然而，在已发表的相互矛盾的结果背景下，必须假定存在潜在的基因修饰因子。这些可能有助于解释关于EGCG的研究结果的总体变异性。不过，我们的数据确实表明，像EGCG这样的天然化合物原则上可以调节大脑可塑性。
