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，这表明脊髓损伤是一种严重的损伤。 学习是功能恢复的内在组成部分。生理和分子机制， 哪种重复活动可以增强脊髓损伤受试者的运动学习仍然是未知的。我们 目前的研究清楚地表明，运动对与突触有关的选定分子系统有影响， 可塑性是学习和记忆的基础特别是，运动会提高脊髓中的BDNF。几 研究已经证明了BDNF对突触易化和神经元兴奋性的有效作用， 这表明BDNF具有介导高级神经功能如学习和记忆的能力。在 事实上，我们最近发现运动诱导的BDNF产生促进海马的学习。在 此外，大量的工作已经证明了BDNF减轻神经损失的治疗潜力 与神经创伤或疾病有关。因此，本提案的一个中心主题是审查 运动诱导的BDNF与脊髓学习能力之间的关系我们建议进行研究， 运动如何通过激活信号系统来促进脊髓的学习， 内源性BDNF和NT-3。要实现这一目标，我们将依靠我们在开拓中取得的经验 目前对运动诱导的BDNF参与介导突触可塑性的理解， 学习我们将使用定义明确的定量行为范式来评估脊髓学习。我们 假设运动和学习共享分子机制，BDNF在运动和学习中起核心作用。 调节受损脊髓中的这些机制。这些研究的亮点是， 评估运动对学习的影响，以及它对同一时间内的踏步表现的影响。 动物我们将利用多巴胺能系统的药理学来促进运动， 完全横断动物，以及它与BDNF系统的密切相互作用。成功的建议 研究应该为治疗的发展提供新的策略，以改善功能恢复 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.