Institute of Pathology, School of Veterinary Sciences, National University of La Plata, La Plata 1900, Argentina.
Neuroscience. 2011 Mar 17;177:195-206. doi: 10.1016/j.neuroscience.2011.01.013. Epub 2011 Jan 14.
Insulin-like growth factor-I (IGF-I) is a powerful neuroprotective molecule in the brain and spinal cord. We have previously shown that intracerebroventricular (i.c.v.) IGF-I gene therapy is an effective strategy to increase IGF-I levels in the cerebrospinal fluid (CSF). Since aging in rats is associated with severe motor function deterioration, we implemented i.c.v. IGF-I gene therapy in very old rats (30-31 months) and assessed the beneficial impact on motor performance. We used recombinant adenovectors (RAds) expressing either green fluorescent protein (GFP) or rat IGF-I. Injection in the lateral or fourth ventricle led to high transgene expression in the ependymal cell layer in the brain and cervical spinal cord. RAd-IGF-I-injected rats but not RAd-GFP-injected controls, showed significantly increased levels of CSF IGF-I. Motor tests showed the expected age-related decline in aged rats. Seventeen-day IGF-I gene therapy induced a significant improvement in motor performance in the aged but not in the young animals. These results show that IGF-I is an effective restorative molecule in the aging brain and spinal cord. The data also reveal that the ependymal route constitutes a promising approach for implementing protective IGF-I gene therapy in the aging CNS.
胰岛素样生长因子-I（IGF-I）是大脑和脊髓中一种强大的神经保护分子。我们之前的研究表明，脑室内（i.c.v.）IGF-I 基因治疗是一种增加脑脊液（CSF）中 IGF-I 水平的有效策略。由于大鼠的衰老与严重的运动功能恶化有关，我们在非常老的大鼠（30-31 个月）中实施了脑室内 IGF-I 基因治疗，并评估了对运动性能的有益影响。我们使用表达绿色荧光蛋白（GFP）或大鼠 IGF-I 的重组腺病毒（RAds）。向侧脑室或第四脑室注射导致大脑和颈脊髓室管膜细胞层中的转基因高表达。RAd-IGF-I 注射的大鼠，但不是 RAd-GFP 注射的对照组，CSF IGF-I 水平显著增加。运动测试显示，老年大鼠出现了预期的与年龄相关的下降。17 天的 IGF-I 基因治疗使老年动物的运动性能显著改善，但对年轻动物没有改善。这些结果表明，IGF-I 是衰老大脑和脊髓中的一种有效的修复分子。这些数据还表明，室管膜途径是在衰老的中枢神经系统中实施保护性 IGF-I 基因治疗的一种有前途的方法。
