Reeve-Irvine Research Center, Sue and Bill Gross Stem Cell Research Center, School of Medicine, University of California at Irvine, Irvine, California 92697-4292, USA.
J Neurotrauma. 2010 Jul;27(7):1333-42. doi: 10.1089/neu.2010.1285.
This study characterizes a model of motor neuron (MN) loss on the molecular, cellular, and behavioral levels. Injection of the toxic lectin Ricinus communis agglutinin I (RCA I or ricin) caused cellular deficit and loss of function by damaging the sciatic nerve. Since the sciatic nerve supplies movement to most of the lower limb, damaging this motor system models lower limb paralysis and the deficits that occur in diseases like amyotrophic lateral sclerosis (ALS) and infantile progressive spinal muscular atrophy (SMA). We used motor-, sensorimotor-, locomotor-, and reflex-based tests to demonstrate loss of function after ricin injection. Loss of function was also demonstrated by decreased retrograde transport, and supported by measurements of muscle wasting. Histochemical and molecular methods were used to characterize sciatic nerve damage in axons and cell bodies, including apoptotic cell death in MNs. This battery of tests documents the extent of the ricin-induced damage and provides a baseline that can be used to judge the efficacy of MN treatment strategies in preclinical studies.
本研究从分子、细胞和行为水平上描述了运动神经元 (MN) 丧失的模型。通过损伤坐骨神经，有毒凝集素蓖麻凝集素 I（RCA I 或蓖麻毒素）的注射导致细胞缺陷和功能丧失。由于坐骨神经为下肢的大部分提供运动，因此损伤该运动系统模拟了下肢瘫痪以及肌萎缩侧索硬化症（ALS）和婴儿进行性脊髓性肌萎缩症（SMA）等疾病中出现的缺陷。我们使用运动、感觉运动、运动和反射为基础的测试来证明注射蓖麻毒素后功能丧失。逆行运输的减少也证明了功能丧失，并且通过肌肉萎缩的测量得到支持。组织化学和分子方法用于描述坐骨神经轴突和细胞体中的损伤，包括 MN 中的凋亡细胞死亡。该组测试记录了蓖麻毒素诱导的损伤程度，并提供了一个基线，可以用于判断临床前研究中 MN 治疗策略的疗效。
