Department of Health and Sports Science, Nippon Medical School, 2-297-2 Kosugi-cho, Nakahara-ku, Kawasaki, Kanagawa 211-0063, Japan.
Neuroscience. 2012 Apr 5;207:208-17. doi: 10.1016/j.neuroscience.2012.01.023. Epub 2012 Jan 20.
In animals, chronic stress leads to the development of depression-like behavior and decreases neurogenesis and blood vessel density in hippocampus, whereas antidepressants increase adult neurogenesis in hippocampus. Regular exercise training also has antidepressant action and increases hippocampal neurogenesis; however, whether exercise-induced antidepressant action is related to hippocampal microvasculature is unclear. To address this issue, we compared depression-like behavior, blood vessel density, and neurogenesis in hippocampal dentate gyrus between stressed and exercised mice with or without administration of inhibitor of vascular endothelial growth factor (VEGF) receptor. Chronic stress led to the development of depression-like behavior, decreased blood vessel density, and neurogenesis in hippocampus. Regular exercise training improved depression-like behavior, the decrease of hippocampal blood vessel density, and neurogenesis in the stress state, whereas the combination of regular exercise and administration of SU1498, VEGF receptor Flk-1 inhibitor, canceled the exercise-induced antidepressant effect. These findings suggested that the improvement of hippocampal blood vessel and adult neurogenesis via VEGF signaling pathway is necessary for exercise-induced antidepressant effect.
在动物中，慢性应激会导致类似抑郁的行为的发展，并减少海马体中的神经发生和血管密度，而抗抑郁药则会增加海马体中的成年神经发生。有规律的运动训练也具有抗抑郁作用，并增加海马体的神经发生；然而，运动引起的抗抑郁作用是否与海马体微血管有关尚不清楚。为了解决这个问题，我们比较了应激和运动小鼠（或不给予血管内皮生长因子（VEGF）受体抑制剂）的海马齿状回的类似抑郁行为、血管密度和神经发生。慢性应激导致类似抑郁的行为、海马体血管密度和神经发生的减少。有规律的运动训练改善了应激状态下的类似抑郁行为、海马体血管密度和神经发生的减少，而有规律的运动和给予 SU1498（VEGF 受体 Flk-1 抑制剂）的组合则取消了运动引起的抗抑郁作用。这些发现表明，通过 VEGF 信号通路改善海马体血管和成年神经发生对于运动引起的抗抑郁作用是必要的。
