Trejo J L, Llorens-Martín M V, Torres-Alemán I
Cajal Institute, CSIC, Doctor Arce 37, 28002 Madrid, Spain.
Mol Cell Neurosci. 2008 Feb;37(2):402-11. doi: 10.1016/j.mcn.2007.10.016. Epub 2007 Nov 5.
Knowledge about the effects of physical exercise on brain is accumulating although the mechanisms through which exercise exerts these actions remain largely unknown. A possible involvement of adult hippocampal neurogenesis (AHN) in the effects of exercise is debated while the physiological and pathological significance of AHN is under intense scrutiny. Recently, both neurogenesis-dependent and independent mechanisms have been shown to mediate the effects of physical exercise on spatial learning and anxiety-like behaviors. Taking advantage that the stimulating effects of exercise on AHN depend among others, on serum insulin-like growth factor I (IGF-I), we now examined whether the behavioral effects of running exercise are related to variations in hippocampal neurogenesis, by either increasing or decreasing it according to serum IGF-I levels. Mutant mice with low levels of serum IGF-I (LID mice) had reduced AHN together with impaired spatial learning. These deficits were not improved by running. However, administration of exogenous IGF-I ameliorated the cognitive deficit and restored AHN in LID mice. We also examined the effect of exercise in LID mice in the novelty-suppressed feeding test, a measure of anxiety-like behavior in laboratory animals. Normal mice, but not LID mice, showed reduced anxiety after exercise in this test. However, after exercise, LID mice did show improvement in the forced swim test, a measure of behavioral despair. Thus, many, but not all of the beneficial effects of exercise on brain function depend on circulating levels of IGF-I and are associated to increased hippocampal neurogenesis, including improved cognition and reduced anxiety.
尽管运动发挥这些作用的机制在很大程度上仍不清楚，但有关体育锻炼对大脑影响的知识正在不断积累。成人海马神经发生（AHN）在运动影响中的可能作用存在争议，而AHN的生理和病理意义正在受到密切关注。最近，已证明神经发生依赖性和非依赖性机制均介导体育锻炼对空间学习和焦虑样行为的影响。利用运动对AHN的刺激作用尤其取决于血清胰岛素样生长因子I（IGF-I）这一特点，我们现在通过根据血清IGF-I水平增加或减少海马神经发生，来研究跑步运动的行为效应是否与海马神经发生的变化有关。血清IGF-I水平低的突变小鼠（LID小鼠）的AHN减少，同时空间学习受损。跑步并未改善这些缺陷。然而，给予外源性IGF-I可改善LID小鼠的认知缺陷并恢复AHN。我们还在新奇抑制摄食试验中研究了运动对LID小鼠的影响，该试验是实验室动物焦虑样行为的一种测量方法。在该试验中，正常小鼠而非LID小鼠在运动后焦虑减轻。然而，运动后，LID小鼠在强迫游泳试验（一种行为绝望的测量方法）中确实表现出改善。因此，运动对脑功能的许多（但不是全部）有益作用取决于循环中的IGF-I水平，并与海马神经发生增加有关，包括改善认知和减轻焦虑。
