Max-Delbrück-Center for Molecular Medicine, 13125, Berlin, Germany.
Charité, University Medicine Berlin, Berlin, Germany.
Cell Mol Life Sci. 2018 Oct;75(19):3625-3634. doi: 10.1007/s00018-018-2815-y. Epub 2018 Apr 20.
Physical exercise induces cell proliferation in the adult hippocampus in rodents. Serotonin (5-HT) and angiotensin (Ang) II are important mediators of the pro-mitotic effect of physical activity. Here, we examine precursor cells in the adult brain of mice lacking angiotensin-converting enzyme (ACE) 2, and explore the effect of an acute running stimulus on neurogenesis. ACE2 metabolizes Ang II to Ang-(1-7) and is essential for the intestinal uptake of tryptophan (Trp), the 5-HT precursor. In ACE2-deficient mice, we observed a decrease in brain 5-HT levels and no increase in the number of BrdU-positive cells following exercise. Targeting the Ang II/AT1 axis by blocking the receptor, or experimentally increasing Trp/5-HT levels in the brain of ACE2-deficient mice, did not rescue the running-induced effect. Furthermore, mice lacking the Ang-(1-7) receptor, Mas, presented a normal neurogenic response to exercise. Our results identify ACE2 as a novel factor required for exercise-dependent modulation of adult neurogenesis and essential for 5-HT metabolism.
体育锻炼可诱导啮齿动物成年海马体中的细胞增殖。5-羟色胺（5-HT）和血管紧张素（Ang）II 是体育活动促有丝分裂作用的重要介质。在这里，我们研究了缺乏血管紧张素转换酶（ACE）2 的小鼠成年大脑中的前体细胞，并探讨了急性跑步刺激对神经发生的影响。ACE2 将 Ang II 代谢为 Ang-(1-7)，并且是肠道摄取色氨酸（Trp）（5-HT 的前体）所必需的。在 ACE2 缺陷型小鼠中，我们观察到运动后大脑 5-HT 水平下降，BrdU 阳性细胞数量无增加。通过阻断受体靶向 Ang II/AT1 轴，或在 ACE2 缺陷型小鼠的大脑中实验性地增加 Trp/5-HT 水平，都不能挽救跑步引起的效应。此外，缺乏 Ang-(1-7) 受体 Mas 的小鼠对运动的神经发生反应正常。我们的结果表明 ACE2 是一种新型因子，是运动依赖性调节成年神经发生所必需的，并且对 5-HT 代谢至关重要。
