Neurotrophins Support Spinal Cord Learning and Rehabilitation

最近的研究表明，受伤的脊髓具有学习运动任务的能力，这表明脊髓 学习是功能恢复的内在组成部分。其生理和分子机制主要包括 在脊髓损伤的受试者中，哪些重复的活动可以增强运动学习仍然难以捉摸。我们的 目前的研究清楚地表明，运动对涉及突触的特定分子系统有影响 学习和记忆的可塑性。特别是，运动会增加脊髓中的脑源性神经营养因子。几个 研究表明，BDNF在突触易化和神经元兴奋性方面具有强大的作用。 提示脑源性神经营养因子具有调节学习记忆等高阶神经功能的功能。在……里面 事实上，我们最近已经表明，运动诱导的BDNF的产生促进了海马体的学习。在……里面 此外，大量工作已经证明了脑源性神经营养因子在减轻神经损失方面的治疗潜力。 与神经创伤或疾病有关。因此，这项提案的一个中心主题是审查 运动性脑源性神经营养因子与脊髓学习的关系我们建议进行研究以确定 运动如何通过激活信号系统来促进脊髓中的学习 内源性脑源性神经营养因子和神经营养因子-3。为了实现这一目标，我们将依靠开拓的经验。 运动性脑源性神经营养因子参与介导突触可塑性的研究现状 学习。我们将使用定义明确的量化行为范式来评估脊髓学习。我们 假设运动和学习具有共同的分子机制，并且BDNF在 在受损的脊髓中调节这些机制。这些研究的亮点是有可能 评估运动对学习的影响，以及它对步态表现的影响 动物。我们将利用5-羟色胺能系统的药理学来促进 完整的横断体动物及其与脑源性神经营养因子系统的密切相互作用。在建议中取得成功 研究应该为改善功能恢复的治疗方法的发展提供新的策略 在脊髓损伤后。

Recent studies showing that the injured spinal cord has the capacity to learn motor tasks, suggest that spinal learning is an intrinsic component of functional recovery. The physiological and molecular mechanisms by which repeated activity can enhance locomotor learning in spinal cord injured subjects remain elusive. Our current research clearly indicates that exercise has an effect on select molecular systems involved with synaptic plasticity underlying learning and memory. In particular, exercise elevates BDNF in the spinal cord. Several studies have demonstrated the potent effect of BDNF on synaptic facilitation and neuronal excitability, indicating that BDNF has the capacity to mediate higher order neural function such as learning and memory. In fact, we have recently shown that exercise-induced BDNF production facilitates hippocampal learning. In addition, a large body of work has demonstrated the therapeutic potential of BDNF to attenuate neural loss associated with neural trauma or disease. Therefore, a central theme of this proposal is to examine the relationship between exercise-induced BDNF and learning in the spinal cord. We propose studies to determine how exercise can facilitate learning in the spinal cord by activating signaling systems under the modulation of endogenous BDNF and NT-3. To accomplish this goal, we will rely on our experience gained from pioneering the current understanding of the involvement of exercise-induced BDNF in mediating synaptic plasticity and learning. We will use a well-defined quantitative behavioral paradigm to assess spinal cord learning. We hypothesize that exercise and learning share molecular mechanisms and that BDNF plays a central role in modulating these mechanisms in the injured spinal cord. The highlight of these studies is the possibility to evaluate the effects of exercise on learning, in conjunction with its effects on stepping performance in the same animals. We will take advantage of the pharmacology of the serotonergic system to facilitate locomotion in complete transected animals, and its close interaction with the BDNF system. Success in the proposed investigations should provide new strategies for the development of treatments to improve functional recovery after spinal cord injury.