Department of Integrative Biology and Physiology, UCLA Brain Injury Research Center, University of California, Los Angeles, CA 90095, USA.
Neuroscience. 2011 Sep 29;192:773-80. doi: 10.1016/j.neuroscience.2011.06.032. Epub 2011 Jun 29.
Exercise has been shown to impact brain plasticity and function by involving the action of brain-derived neurotrophic factor (BDNF); however, mechanisms involved are poorly understood. Two types of BDNF coexist in the brain, the precursor (proBDNF) and its mature product (mBDNF), which preferentially bind specific receptors and exert distinct functions. It is crucial to understand how exercise affects crucial steps in the BDNF processing and signaling to evaluate therapeutic applications. We found that 7 days of voluntary exercise increased both pro and mature BDNF in the rat hippocampus. Exercise also increased the activity of tissue-type plasminogen activator (tPA), a serine proteinase shown to facilitate proBDNF cleavage into mBDNF. The blockade of tPA activity reduced the exercise effects on proBDNF and mBDNF. The tPA blocking also inhibited the activation of TrkB receptor, and the TrkB signaling downstream effectors phospho-ERK, phospho-Akt, and phospho-CaMKII. The blocking of tPA also counteracted the effects of exercise on the plasticity markers phospho-synapsin I and growth-associated protein 43 (GAP-43). These results indicate that the effects of exercise on hippocampal plasticity are dependent on BDNF processing and subsequent TrkB signaling, with important implications for neuronal function.
运动通过脑源性神经营养因子（BDNF）的作用来影响大脑的可塑性和功能；然而，其涉及的机制仍不清楚。脑内存在两种类型的 BDNF，前体（proBDNF）和成熟产物（mBDNF），它们优先结合特定的受体并发挥不同的功能。了解运动如何影响 BDNF 加工和信号传递的关键步骤对于评估治疗应用至关重要。我们发现，7 天的自愿运动增加了大鼠海马体中的 pro 和成熟 BDNF。运动还增加了组织型纤溶酶原激活物（tPA）的活性，tPA 是一种丝氨酸蛋白酶，被证明能促进 proBDNF 切割成 mBDNF。tPA 活性的阻断减少了运动对 proBDNF 和 mBDNF 的影响。tPA 阻断也抑制了 TrkB 受体的激活，以及 TrkB 信号下游效应物磷酸化-ERK、磷酸化-Akt 和磷酸化-CaMKII。tPA 的阻断也抵消了运动对可塑性标志物磷酸化突触素 I 和生长相关蛋白 43（GAP-43）的影响。这些结果表明，运动对海马体可塑性的影响依赖于 BDNF 加工和随后的 TrkB 信号传递，这对神经元功能有重要意义。
