AIMS Mutations in DNA/RNA-binding factor (fused-in-sarcoma) FUS and superoxide dismutase-1 (SOD-1) cause amyotrophic lateral sclerosis (ALS). They were reproduced in SOD-1-G93A (SOD-1) and new FUS[1-359]-transgenic (FUS-tg) mice, where inflammation contributes to disease progression. The effects of standard disease therapy and anti-inflammatory treatments were investigated using these mutants. METHODS FUS-tg mice or controls received either vehicle, or standard ALS treatment riluzole (8 mg/kg/day), or anti-inflammatory drug a selective blocker of cyclooxygenase-2 celecoxib (30 mg/kg/day) for six weeks, or a single intracerebroventricular (i.c.v.) infusion of Neuro-Cells (a preparation of 1.39 × 106 mesenchymal and hemopoietic human stem cells, containing 5 × 105 of CD34+ cells), which showed anti-inflammatory properties. SOD-1 mice received i.c.v.-administration of Neuro-Cells or vehicle. RESULTS All FUS-tg-treated animals displayed less marked reductions in weight gain, food/water intake, and motor deficits than FUS-tg-vehicle-treated mice. Neuro-Cell-treated mutants had reduced muscle atrophy and lumbar motor neuron degeneration. This group but not celecoxib-FUS-tg-treated mice had ameliorated motor performance and lumbar expression of microglial activation marker, ionized calcium-binding adapter molecule-1 (Iba-1), and glycogen-synthase-kinase-3ß (GSK-3ß). The Neuro-Cells-treated-SOD-1 mice showed better motor functions than vehicle-treated-SOD-1 group. CONCLUSION The neuropathology in FUS-tg mice is sensitive to standard ALS treatments and Neuro-Cells infusion. The latter improves motor outcomes in two ALS models possibly by suppressing microglial activation.

中文翻译：

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神经细胞疗法可改善小鼠肌萎缩侧索硬化实验综合征期间的运动结果并抑制炎症。

AIMS DNA/RNA 结合因子（融合肉瘤）FUS 和超氧化物歧化酶-1 (SOD-1) 中的突变会导致肌萎缩侧索硬化 (ALS)。它们在 SOD-1-G93A (SOD-1) 和新的 FUS[1-359]-转基因 (FUS-tg) 小鼠中复制，其中炎症有助于疾病进展。使用这些突变体研究了标准疾病治疗和抗炎治疗的效果。方法 FUS-tg 小鼠或对照接受载体或标准 ALS 治疗利鲁唑（8 毫克/公斤/天），或抗炎药，环加氧酶-2 塞来昔布的选择性阻断剂（30 毫克/公斤/天），持续六周，或单次脑室内 (icv) 输注神经细胞（1.39 × 106 间充质和造血人类干细胞的制剂，含有 5 × 105 CD34+ 细胞），显示抗炎特性。SOD-1 小鼠接受 icv - 神经细胞或载体的给药。结果 与 FUS-tg-载体治疗的小鼠相比，所有 FUS-tg 治疗的动物在体重增加、食物/水摄入量和运动缺陷方面的减少都不那么明显。神经细胞治疗的突变体减少了肌肉萎缩和腰椎运动神经元变性。这组而非塞来昔布-FUS-tg 治疗的小鼠改善了小胶质细胞激活标记物、离子钙结合接头分子-1 (Iba-1) 和糖原合酶-激酶-3ß (GSK-3ß) 的运动表现和腰椎表达）。神经细胞处理的 SOD-1 小鼠表现出比媒介物处理的 SOD-1 组更好的运动功能。结论 FUS-tg 小鼠的神经病理学对标准 ALS 治疗和神经细胞输注敏感。后者可能通过抑制小胶质细胞激活来改善两个 ALS 模型的运动结果。