Department of Physiology and Biophysics, Institute of Biology, State University of Campinas (UNICAMP), P.O. Box 6109, 13083-970 Campinas, São Paulo, Brazil.
Neuroscience. 2011 Apr 28;180:9-18. doi: 10.1016/j.neuroscience.2011.02.055. Epub 2011 Mar 1.
Clinical studies show an evident antidepressive effect of physical exercise and animal research corroborate such evidence. However, the neurobiological mechanisms underlying the antidepressive effect of exercise are not completely understood. Notwithstanding, it is known that exercise increases brain-derived neurotrophic factor (BDNF) expression in the hippocampus similarly to antidepressant drugs. BDNF is synthesized as a precursor molecule that undergoes a proteolytic cleavage to generate either a mature or a truncated isoform. Precursor and mature BDNF are assumed to elicit opposing biological effects in neuroplasticity. In the present study we investigated the effect of voluntary physical activity on precursor and mature brain-derived neurotrophic factor levels and on proBDNF cleavage related genes, p11 and tissue plasminogen activator (tPA), as well as the antidepressive and cognitive effects of voluntary physical activity. Mice had access to mobile or locked running wheels for 28 days and were submitted to forced-swim, tail suspension and water maze tests. Their hippocampi were dissected and analyzed by Western blot and real time RT-PCR. Voluntary physical activity, but not locked wheel exposure, induced a robust increase in hippocampal mature BDNF protein levels, as well as in p11 and tPA mRNA expression; and also promoted antidepressive effects and improved learning, when compared with sedentary mice. On the other hand, there were no significant differences between any groups in the expression of precursor or truncated isoforms of BDNF. Our data suggest that the antidepressive effect of the physical exercise may depend, at least in part, on changes in BDNF post-translational processing.
临床研究表明，体育锻炼具有明显的抗抑郁作用，动物研究也证实了这一证据。然而，运动抗抑郁作用的神经生物学机制尚不完全清楚。尽管如此，已知运动可增加海马体中的脑源性神经营养因子（BDNF）表达，与抗抑郁药物的作用相似。BDNF 作为前体分子合成，经历蛋白水解切割，生成成熟或截断的同工型。前体和成熟的 BDNF 被认为在神经可塑性中产生相反的生物学效应。在本研究中，我们研究了自愿体力活动对前体和成熟脑源性神经营养因子水平以及 proBDNF 切割相关基因 p11 和组织型纤溶酶原激活物（tPA）的影响，以及自愿体力活动的抗抑郁和认知作用。小鼠有机会使用移动或锁定的跑步轮 28 天，并接受强迫游泳、悬尾和水迷宫测试。他们的海马体被解剖并通过 Western blot 和实时 RT-PCR 进行分析。与久坐不动的小鼠相比，自愿体力活动（而非锁定轮暴露）可显著增加海马体中成熟 BDNF 蛋白水平，以及 p11 和 tPA mRNA 的表达；并促进抗抑郁作用和学习能力的提高。另一方面，在任何组之间，BDNF 前体或截断同工型的表达均无显著差异。我们的数据表明，运动的抗抑郁作用可能至少部分取决于 BDNF 翻译后加工的变化。
