Department of Physiological Science, UCLA, Box 951606, Los Angeles, CA 90095-1606, USA.
Exp Neurol. 2010 Mar;222(1):59-69. doi: 10.1016/j.expneurol.2009.12.008. Epub 2009 Dec 16.
Transplantation of olfactory bulb-derived olfactory ensheathing glia (OEG) combined with step training improves hindlimb locomotion in adult rats with a complete spinal cord transection. Spinal cord injury studies use the presence of noradrenergic (NA) axons caudal to the injury site as evidence of axonal regeneration and we previously found more NA axons just caudal to the transection in OEG- than media-injected spinal rats. We therefore hypothesized that OEG transplantation promotes descending coeruleospinal regeneration that contributes to the recovery of hindlimb locomotion. Now we report that NA axons are present throughout the caudal stump of both media- and OEG-injected spinal rats and they enter the spinal cord from the periphery via dorsal and ventral roots and along large penetrating blood vessels. These results indicate that the presence of NA fibers in the caudal spinal cord is not a reliable indicator of coeruleospinal regeneration. We then asked if NA axons appose cholinergic neurons associated with motor functions, i.e., central canal cluster and partition cells (active during fictive locomotion) and somatic motor neurons (SMNs). We found more NA varicosities adjacent to central canal cluster cells, partition cells, and SMNs in the lumbar enlargement of OEG- than media-injected rats. As non-synaptic release of NA is common in the spinal cord, more associations between NA varicosities and motor-associated cholinergic neurons in the lumbar spinal cord may contribute to the improved treadmill stepping observed in OEG-injected spinal rats. This effect could be mediated through direct association with SMNs and/or indirectly via cholinergic interneurons.
嗅球源性嗅鞘胶质细胞（OEG）移植联合阶梯训练可改善完全性脊髓横断大鼠后肢运动功能。脊髓损伤研究将损伤部位以下去甲肾上腺素能（NA）轴突的存在作为轴突再生的证据，我们之前发现 OEG 注射组大鼠损伤部位以下 NA 轴突比介质注射组大鼠更多。因此，我们假设 OEG 移植促进了下行蓝斑脊髓再生，有助于后肢运动功能的恢复。现在我们报告说，介质和 OEG 注射脊髓大鼠的尾部残端都存在 NA 轴突，它们通过背根和腹根以及大的穿透血管从外周进入脊髓。这些结果表明，尾部脊髓中 NA 纤维的存在并不能可靠地指示蓝斑脊髓再生。然后我们询问 NA 轴突是否与与运动功能相关的胆碱能神经元（即中央管簇和分隔细胞（在虚构运动期间活跃）和躯体运动神经元（SMN））接近。我们发现 OEG 注射组大鼠腰膨大处 NA 末梢旁的中央管簇细胞、分隔细胞和 SMN 比介质注射组大鼠更多。由于 NA 的非突触释放在脊髓中很常见，因此在脊髓中 NA 末梢与运动相关的胆碱能神经元之间可能存在更多的关联，这可能有助于改善 OEG 注射脊髓大鼠在跑步机上的踏步运动。这种效应可能通过与 SMN 的直接关联和/或通过胆碱能中间神经元的间接关联来介导。
