Re-expression of L1 CAM Following Spinal Cord Injury

描述（由申请人提供）： L1是一种轴突细胞粘附分子（CAM）， 轴突在发育过程中生长，但在成年期下降到低水平。会 CAM在哺乳动物中是高度保守的，相关分子在多种哺乳动物中被发现。 物种，这表明其在轴突寻路功能的保守性， 肌束震颤L1由嗅鞘神经胶质细胞（OEG）和雪旺氏细胞表达。 细胞，两者都促进轴突再生。此外，L1是 在海马结构的再生轴突上重新表达。因此，L1是 粘附型分子的优秀候选者， 再生脊髓轴突具体目标1是确定棘上 靶点是在大脑上表达Ll的GABA能连合神经元群体 轴突的表面。接下来的实验将检查轴突 这些连合神经元在L1敲除小鼠中的路径发现。具体目标2 试图确定L1是否在成体轴突再生新的轴突时在成体轴突上重新表达 脊髓损伤（SCI）后的过程。在一个完整的胸中部 脊髓横切在出生后第5天，我们有初步的数据表明， L1在病变的头侧和尾侧的轴突中重新表达 受伤后的几个月我们将表征Ll在轴突上的时间表达， 相对于受伤后的时间，以提供关于潜在的 脊髓损伤后轴突出芽。此外，我们将测试是否训练脊柱 以脊柱步进模式横切的动物将改变L1的水平 在受损轴突上的表达。在特定目标3中，OEG移植模型 将被用来确定上升的感觉轴突是否能够投射到 它们的目标，如果上升和下降再生轴突将 当它们穿过横切位点时重新表达L1CAM。脊髓横断动物 将用表达L1的OEG细胞移植，而对照将用表达L1的OEG细胞移植。 注入介质。这种OEG移植模型已被其他人证明， 显著改善SCI成年动物的自主运动功能。我们 长期目标是开发一种SCI再生模型， 来自连合神经元的上行投射

DESCRIPTION (provided by applicant): L1 is an axonal cell adhesion molecule (CAM) that is highly expressed on growing axons during development but decreases to low levels by adulthood. Ll CAM is highly conserved in mammals, and related molecules are found in diverse species, suggesting a conservation of its function in axonal pathfinding and fasciculation. L1 is expressed by olfactory ensheathing glia (OEG) and Schwann cells, both of which facilitate axon regeneration. In addition, Ll is re-expressed on regenerating axons in the hippocampal formation. Thus, Ll is an excellent candidate for an adhesion type molecule of critical importance to regenerating spinal cord axons. Specific Aim 1 is to determine the supraspinal target of a population of GABAergic commissural neurons that express Ll on the surface of their axons. Subsequent experiments will examine the axonal pathfinding of these commissural neurons in Ll knockout mice. Specific Aim 2 seeks to determine if Ll is re-expressed on adult axons as they regenerate new processes after spinal cord injury (SCI). Following a complete midthoracic spinal cord transection at postnatal day 5, we have preliminary data suggesting that Ll is re-expressed in axons both rostral and caudal to the lesion three months post injury. We will characterize the temporal expression of Ll on axons relative to the time post injury to provide information regarding potential axon sprouting after SCI. Furthermore, we will test if training spinal transected animals in spinal stepping patterns will change the level of Ll expression on lesioned axons. In Specific Aim 3, an OEG transplantation model will be used to determine if ascending sensory axons are able to project to their targets and if ascending and descending regenerating axons will re-express Ll CAM as they cross the transection site. Spinal transected animals will be transplanted with Ll-expressing OEG cells, whereas the controls will be injected with media. This OEG transplantation model has been shown by others to dramatically improve voluntary motor function in adult animals with SCI. Our long term goal is to develop a regeneration model for SCI that restores the ascending projections from commissural neurons.