Ohta Yasuyuki, Nagai Makiko, Nagata Tetsuya, Murakami Tetsuro, Nagano Isao, Narai Hisashi, Kurata Tomoko, Shiote Mito, Shoji Mikio, Abe Koji
Department of Neurology, Graduate School of Medicine, Dentistry and Pharmacy, Okayama University, Okayama, Japan.
J Neurosci Res. 2006 Oct;84(5):980-92. doi: 10.1002/jnr.21017.
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 dismutase (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 (Iba1), 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.
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）至正常和有症状的携带突变人铜/锌超氧化物歧化酶（SOD1）基因的转基因（Tg）小鼠腰段脊髓区域后，肌萎缩侧索硬化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，与非Tg小鼠相比，Tg小鼠脊髓中5-溴脱氧尿苷（BrdU）+巢蛋白双标记的神经前体细胞增加，EGF和FGF2处理使其增加幅度更大。BrdU+巢蛋白双标记细胞的数量大于BrdU+离子钙结合衔接分子1（Iba1）、BrdU+胶质纤维酸性蛋白（GFAP）或BrdU+高度多聚唾液酸化神经细胞黏附分子（PSA-NCAM）双标记细胞的数量，但均不表达神经元核抗原（NeuN）。进一步分析Tg小鼠的灰质，BrdU+巢蛋白和BrdU+PSA-NCAM双标记细胞在腹角的增加比背角更多，EGF和FGF2处理再次使其显著增加。由于神经前体细胞位于中央管室管膜附近，本研究表明，有症状的Tg小鼠中神经前体细胞向腹角的增殖和迁移被极大激活，EGF和FGF2处理进一步增强，此外，在接受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非星形胶质细胞。
