Max-Delbruck-Center for Molecular Medicine, 13125 Berlin, Germany.
J Neurosci. 2013 May 8;33(19):8270-5. doi: 10.1523/JNEUROSCI.5855-12.2013.
Voluntary wheel running has long been known to induce precursor cell proliferation in adult hippocampal neurogenesis in rodents. However, mechanisms that couple activity with the promitotic effect are not yet fully understood. Using tryptophan hydroxylase (TPH) 2 deficient (Tph2-deficient) mice that lack brain serotonin, we explored the relationship between serotonin signaling and exercise-induced neurogenesis. Surprisingly, Tph2-deficient mice exhibit normal baseline hippocampal neurogenesis but impaired activity-induced proliferation. Our data demonstrate that the proproliferative effect of running requires the release of central serotonin in young-adult and aged mice. Lack of brain serotonin further results in alterations at the stage of Sox2-positive precursor cells, suggesting physiological adaptations to changes in serotonin supply to maintain homeostasis in the neurogenic niche. We conclude that serotonin plays a direct and acute regulatory role in activity-dependent hippocampal neurogenesis. The understanding of exercise-induced neurogenesis might offer preventive but also therapeutic opportunities in depression and age-related cognitive decline.
自愿转轮运动长期以来被认为可以诱导成年海马神经发生中的前体细胞增殖。然而，将活动与促有丝分裂作用联系起来的机制尚未完全阐明。我们使用色氨酸羟化酶（TPH）2 缺乏（Tph2 缺乏）的小鼠，这些小鼠缺乏大脑中的血清素，探索了血清素信号与运动诱导的神经发生之间的关系。令人惊讶的是，Tph2 缺乏的小鼠表现出正常的基础海马神经发生，但活动诱导的增殖受损。我们的数据表明，跑步的促增殖作用需要年轻成年和老年小鼠中枢血清素的释放。大脑中缺乏血清素会进一步导致 Sox2 阳性前体细胞阶段的改变，这表明对血清素供应变化的生理适应，以维持神经发生龛中的体内平衡。我们得出结论，血清素在活动依赖性海马神经发生中发挥直接和急性调节作用。对运动诱导的神经发生的理解可能为抑郁症和与年龄相关的认知能力下降提供预防和治疗机会。
