Anti-apoptotic Therapy (Intrathecal Injection of Anti-apoptotic PTD-FNK Protein) in a Mouse Model of Amyotrophic Lateral Sclerosis

我们研究了鞘内注射表皮生长因子(EGF)和成纤维细胞生长因子2(FGF2)到正常和有症状的人铜锌超氧化物歧化酶(SOD1)突变转基因(TG)小鼠腰髓区域的肌萎缩侧索硬化症脊髓中神经前体细胞激活的三个步骤-增殖、迁移和分化。我们观察到转基因小鼠脊髓中5-溴脱氧尿苷(BrdU)巢蛋白双标神经前体细胞较非转基因小鼠增多，且经EGF和FGF2处理后增加幅度更大。BrdU巢蛋白双标细胞数多于BrdU电离钙结合接头分子1(IBAL)、BrdU胶质纤维酸性蛋白(GFAP)。或BrdU高度多唾液酸化的神经细胞黏附分子(.PSA-NCAM.)双标细胞，但无神经元核抗原(NeuN)表达。进一步分析转基因小鼠的灰质，发现BrdU nestin和BrdU PSA-NCAM双标细胞在腹角比背角增加更多。经EGF和FGF2处理后，其表达又显著增强。由于神经前体细胞位于中央管室管膜附近，本研究提示，在有症状的TG小鼠中，神经前体细胞的增殖和向腹角的迁移被极大地激活，并被EGF和FGF2处理进一步促进；此外，在EGF和FGF2处理的TG小鼠中，神经前体细胞优先分化为神经元前体细胞而不是星形胶质细胞。

We investigated three steps of neural precursor cell activation-proliferation, migration, and differentiation.in amyotrophic lateral sclerosis spinal cord treated with intrathecal infusion of epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2) into the lumbar spinal cord region of normal and symptomatic transgenic (Tg) mice with a mutant human Cu/Zn superoxide disniutase (SOD1) gene. We observed that 5-bromodeoxyuridine (BrdU) + nestin double-labeled neural precursor cells increased in the spinal cords of Tg mice compared with non-Tg mice, with a much greater increase produced by EGF and FGF2 treatment. The number of BrdU + nestin double-labeled cells was larger than that of BrdU + ionized calcium-binding adapter molecule.1 (Ibal), BrdU + glial fibrillary acidic protein (GFAP). or BrdU + highly polysialylated neural cell adhesion molecule (.PSA-NCAM.) double-labeled cells, but none expressed neuronal nuclear antigen (NeuN). On further analysis of the gray matter of Tg mice, the number of BrdU + nestin and BrdU + PSA-NCAM double-labeled cells increased more in the ventral horns than the dorsal horns. which was again greatly enhanced by EGF and FGF2 treatment. Because neural precursor cells reside close to the ependyma of central canal, the present study suggests that proliferation and migration of neural precursor cells to the ventral horns is greatly activated in symptomatic Tg mice and is further enhanced by EGF and FGF2 treatment and, furthermore, that the neural precursor cells preferentially differentiate into neuronal precursor cells instead of astrocytes in Tg mice with EGF and FGF2 treatment.