Institute of Cell Biology and Neurobiology, National Research Council, Fondazione S. Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy.
Institute of Cell Biology and Neurobiology, National Research Council, Fondazione S. Lucia, Via del Fosso di Fiorano 64, 00143 Rome, Italy; Department of Ecological and Biological Sciences, University of Tuscia, Largo dell'Università s.n.c., 01100 Viterbo, Italy.
Brain Res Bull. 2018 Oct;143:181-193. doi: 10.1016/j.brainresbull.2018.09.002. Epub 2018 Sep 17.
Of wide interest for health is the relation existing between depression, a very common psychological illness, accompanied by anxiety and reduced ability to concentrate, and adult neurogenesis. We will focus on two neurogenic stimuli, fluoxetine and physical exercise, both endowed with the ability to activate adult neurogenesis in the dentate gyrus of the hippocampus, known to be required for learning and memory, and both able to counteract depression. Fluoxetine belongs to the class of selective serotonin reuptake inhibitor (SSRI) antidepressants, which represent the most used pharmacological therapy; physical exercise has also been shown to effectively counteract depression symptoms in rodents as well as in humans. While there is evidence that the antidepressant effect of fluoxetine requires its pro-neurogenic action, exerted by promoting proliferation, differentiation and survival of progenitor cells of the hippocampus, on the other hand fluoxetine exerts also neurogenesis-independent antidepressant effects by influencing the plasticity of the new neurons generated. Similarly, the antidepressant action of running also correlates with an increase of hippocampal neurogenesis and plasticity, although the gene pathways involved are only partially coincident with those of fluoxetine, such as those involved in serotonin metabolism and synapse formation. We further discuss how extra-neurogenic actions are also suggested by the fact that, unlike running, fluoxetine is unable to stimulate neurogenesis during aging, but still displays antidepressant effects. Moreover, in specific conditions, fluoxetine or running activate not only progenitor but also stem cells, which normally are not stimulated; this fact reveals how stem cells have a long-term, hidden ability to self-renew and, more generally, that neurogenesis is subject to complex controls that may play a role in depression, such as the type of neurogenic stimulus or the state of the local niche. Finally, we discuss how fluoxetine or running are effective in counteracting depression originated from stress or neurodegenerative diseases.
广泛引起健康关注的是抑郁症（一种非常常见的心理疾病，伴有焦虑和注意力集中能力下降）与成人神经发生之间的关系。我们将重点关注两种神经发生刺激物，即氟西汀和体育锻炼，它们都具有激活海马齿状回中的成人神经发生的能力，而海马齿状回是学习和记忆所必需的，并且都能够抵抗抑郁。氟西汀属于选择性 5-羟色胺再摄取抑制剂（SSRI）抗抑郁药，是最常用的药物疗法；体育锻炼也已被证明能有效地抵抗啮齿动物和人类的抑郁症状。虽然有证据表明氟西汀的抗抑郁作用需要其促进海马祖细胞增殖、分化和存活的促神经发生作用，但另一方面，氟西汀通过影响新生成神经元的可塑性，也发挥神经发生独立的抗抑郁作用。同样，跑步的抗抑郁作用也与海马神经发生和可塑性的增加相关，尽管涉及的基因途径与氟西汀的部分重叠，例如涉及 5-羟色胺代谢和突触形成的基因途径。我们进一步讨论了事实表明，除了神经发生作用外，还有其他作用，即与跑步不同，氟西汀不能在衰老过程中刺激神经发生，但仍显示出抗抑郁作用。此外，在特定条件下，氟西汀或跑步不仅能激活祖细胞，还能激活通常不会被刺激的干细胞；这一事实揭示了干细胞具有长期隐藏的自我更新能力，更普遍地说，神经发生受到复杂的控制，这些控制可能在抑郁中发挥作用，例如神经发生刺激的类型或局部生态位的状态。最后，我们讨论了氟西汀或跑步如何有效抵抗应激或神经退行性疾病引起的抑郁。
