Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany; Department of Pharmacology and Therapeutics, Faculty of Medicine, Universitas Sumatera Utara, Medan, 20155, Indonesia.
Center for Regenerative Therapies Dresden (CRTD), Technische Universität Dresden, 01307 Dresden, Germany; German Center for Neurodegenerative Diseases (DZNE) Dresden, 01307 Dresden, Germany; Queensland Brain Institute (QBI), The University of Queensland, Brisbane 4072, Australia.
Stem Cell Reports. 2021 Mar 9;16(3):548-565. doi: 10.1016/j.stemcr.2021.01.005. Epub 2021 Feb 11.
As mammals evolved with exposure to particular diets, naturally abundant compounds may have become part of the set of environmental co-determinants that shaped brain structure and function. Here we investigated whether bioactive factors found in apples directly affect hippocampal neurogenesis in the adult mouse. We found that quercetin, the most abundant flavanol in apple peel, was anti-proliferative at high concentrations but pro-neurogenic at low concentrations. This was confirmed in vivo, with intraperitoneally delivered quercetin promoting survival and neuronal differentiation, without affecting proliferation. Using a bioassay-guided fractionation approach we also identified additional pro-neurogenic compounds in apple flesh that were not related to flavonoids. We found that 3,5-dihydroxybenzoic acid significantly increased neural precursor cell proliferation and neurogenesis. This work shows that both flavonoids and 3,5-dihydroxybenzoic acid are pro-neurogenic, not only by activating precursor cell proliferation but also by promoting cell-cycle exit, cellular survival, and neuronal differentiation.
随着哺乳动物接触特定饮食而进化，天然丰富的化合物可能成为塑造大脑结构和功能的环境共同决定因素的一部分。在这里，我们研究了苹果中发现的生物活性因子是否直接影响成年小鼠海马神经发生。我们发现，槲皮素是苹果皮中含量最丰富的黄烷醇，在高浓度下具有抗增殖作用，但在低浓度下具有促神经发生作用。这在体内得到了证实，腹腔内给予槲皮素可促进存活和神经元分化，而不影响增殖。使用生物测定指导的分级分离方法，我们还在苹果果肉中鉴定出其他与类黄酮无关的促神经发生化合物。我们发现 3,5-二羟基苯甲酸可显著增加神经前体细胞的增殖和神经发生。这项工作表明，类黄酮和 3,5-二羟基苯甲酸不仅通过激活前体细胞增殖，而且通过促进细胞周期退出、细胞存活和神经元分化来促进神经发生。
