Interference with MEK1 signaling to improve nerve sprouting and regeneration

实现脊髓再生是实验神经生物学中主要的实际挑战之一。脊髓损伤患者分为两类。那些不完全性脊髓横断，显示出明显的潜力，相当大的，虽然不是完全恢复，通过分支过程，从未受伤的纤维。在那些完全横断的情况下，由于受伤的纤维无法再生，结果是可怕的。有趣的是，目前的研究对这两组人都有帮助。目前的提议旨在探索受损神经细胞内一种叫做MEK1的关键信号对这些神经元在大脑和脊髓内产生新连接的能力的影响。它将使用经过基因改造的动物，这些动物的神经细胞内活跃的MEK1水平发生了巨大的变化。我们已经知道，这些动物在周围神经受损后更渴望产生神经连接。在当前的提案中要回答的关键问题是，这种能力是否可以用于改善脊髓损伤后的恢复。

Achieving regeneration in the spinal cord represents one of the major practical challenges in experimental neurobiology. There are two groups of patients with spinal cord damage. Those with incomplete spinal cord transection, show a clear potential for considerable though not complete recovery, through a branching-out process from spared, uninjured fibres. In those, with complete transection, the results are dire, due to the inability of injured fibres to regrow. Interestingly, the current work could help in both groups. The current proposal aims at exploring the effects of a key signal called MEK1, inside the injured nerve cell, on the ability to of these neurons to generate new connections inside brain and spinal cord. It will use genetically manipulated animals that have drastically changed levels of active MEK1 inside the nerve cell. We already know that these animals are more eager to generate nerve connections following damage to peripheral nerves. The key question, to be answered in the current proposal, will be whether this ability could be used to improve recovery following spinal cord damage.