Abstract：
Exercise is known to reduce depression and anxiety symptoms. Although the cellular and molecular mechanisms underlying this effect remain unknown, exercise-induced increases in neurotransmitter release and hippocampal neurogenesis have been hypothesized to play key roles. One neurotransmitter that has been implicated in both antidepressant-like effects and the regulation of hippocampal neurogenesis is serotonin (5-HT). Complete loss of function of the brain 5-HT synthesis enzyme (tryptophan hydroxylase 2, Tph2) has been reported to prevent exercise-induced increases in neurogenesis and to block a subset of antidepressant-like responses to selective serotonin reuptake inhibitors (SSRIs), but whether partial loss of Tph2 function blocks the behavioral and neurogenic effects of exercise has not been established. This study used four tests that are predictive of antidepressant efficacy to determine the impact of 5-HT deficiency on responses to exercise in male and female mice. Our results demonstrate that low 5-HT impairs the behavioral effects of exercise in females in the forced swim and novelty-suppressed feeding tests. However, genetic reductions in 5-HT synthesis did not significantly impact exercise-induced alterations in cellular proliferation or immature neuron production in the hippocampus in either sex. These findings highlight the importance of brain 5-HT in mediating behavioral responses to exercise and suggest that individual differences in brain 5-HT synthesis could influence sensitivity to the mental health benefits of exercise. Furthermore, the observed disconnect between neurogenic and behavioral responses to exercise suggests that increased neurogenesis is unlikely to be the primary driver of the behavioral effects of exercise observed here.
摘要：
众所周知，运动可以减轻抑郁和焦虑症状。尽管这种效应背后的细胞和分子机制仍然未知，运动诱导的神经递质释放和海马神经发生的增加被认为起关键作用.5-羟色胺（5-HT）是一种涉及抗抑郁样作用和海马神经发生调节的神经递质。据报道，大脑5-HT合成酶（色氨酸羟化酶2，Tph2）的功能完全丧失可防止运动引起的神经发生增加，并阻断对选择性5-羟色胺再摄取抑制剂（SSRIs）的抗抑郁药样反应。但是Tph2功能的部分丧失是否会阻断运动的行为和神经源性效应尚未确定。这项研究使用了四项预测抗抑郁药效的测试来确定5-HT缺乏对雄性和雌性小鼠运动反应的影响。我们的结果表明，在强迫游泳和新奇抑制喂养测试中，低5-HT会损害女性运动的行为效果。然而,5-HT合成的基因减少对运动诱导的海马细胞增殖或未成熟神经元产生的改变均无显著影响.这些发现强调了大脑5-HT在调节运动行为反应中的重要性，并表明大脑5-HT合成的个体差异可能会影响运动对心理健康益处的敏感性。此外，观察到的神经源性和运动行为反应之间的脱节表明，神经发生增加不太可能是此处观察到的运动行为效应的主要驱动因素。
