Interferon-γ Decreases Chondroitin Sulfate Proteoglycan Expression and Enhances Hindlimb Function after Spinal Cord Injury in Mice
Interferon-γ Decreases Chondroitin Sulfate Proteoglycan Expression and Enhances Hindlimb Function after Spinal Cord Injury in Mice
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DOI：
10.1089/neu.2009.1144
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发表时间：
2010-12-01
影响因子：
4.2
通讯作者：
Yamazaki, Masashi
中科院分区：
文献类型：
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作者：
Fujiyoshi, Takayuki;Kubo, Takekazu;Yamazaki, Masashi
胶质细胞，包括星形胶质细胞和巨噬细胞/小胶质细胞，被认为可以调节脊髓损伤（SCI）后的病理状态。在本研究中，我们评估了干扰素-γ (IFN-γ) 在小鼠挫伤性 SCI 模型中的治疗效果，干扰素是调节神经胶质功能的细胞因子之一。我们发现腹腔注射 IFN-γ 显着促进 SCI 后运动能力的改善。免疫组织化学表明，IFN-γ 减少了硫酸软骨素蛋白聚糖 (CSPG) 的积累，硫酸软骨素蛋白聚糖是受损中枢神经系统 (CNS) 中反应性星形胶质细胞产生的关键轴突生长抑制剂。定量实时聚合酶链反应 (RT-PCR) 和蛋白质印迹表明，与载体治疗的小鼠相比，IFN-γ治疗的小鼠脊髓中的神经聚糖（几种 CSPG 之一）减少。一致地，IFN-γ在体外抑制激活的星形胶质细胞产生神经聚糖。此外，IFN-γ治疗增加了病变中心周围血清素阳性神经纤维和有髓神经纤维的数量。我们还发现，在 IFN-γ 治疗后，脊髓损伤后胶质细胞源性神经营养因子 (GDNF) 和胰岛素样生长因子-1 (IGF-1) 上调。我们的结果表明，IFN-γ 对小鼠挫伤性 SCI 具有治疗作用，可能是通过减少反应性星形胶质细胞的 CSPG 表达并增加神经营养因子的表达来实现的。
Glial cells, including astrocytes and macrophages/microglia, are thought to modulate pathological states following spinal cord injury (SCI). In the present study, we evaluated the therapeutic effects of interferon-gamma (IFN-gamma), which is one of the cytokines regulating glial function, in a mouse contusive SCI model. We found that intraperitoneal injection of IFN-gamma significantly facilitated locomotor improvement following SCI. Immunohistochemistry demonstrated that IFN-gamma decreased the accumulation of chondroitin sulfate proteoglycans (CSPGs), which are critical axon outgrowth inhibitors produced by reactive astrocytes in the injured central nervous system (CNS). Quantitative real-time polymerase chain reaction (RT-PCR) and Western blotting demonstrated that neurocan, one of several CSPGs, was reduced in the spinal cords of IFN-gamma-treated mice compared to vehicle-treated mice. Consistently, IFN-gamma inhibited the production of neurocan from activated astrocytes in vitro. In addition, IFN-gamma treatment enhanced the number of serotonin-positive nerve fibers and myelinated nerve fibers around the lesion epicenter. We also found that glial cell line-derived neurotrophic factor (GDNF) and insulin-like growth factor-1 (IGF-1) were upregulated post-SCI following IFN-gamma treatment. Our results indicate that IFN-gamma exhibits therapeutic effects in mouse contusive SCI, presumably by reducing CSPG expression from reactive astrocytes and increasing the expression of neurotrophic factors.