Insulin‐like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination
Insulin‐like growth factor type 1 receptor signaling in the cells of oligodendrocyte lineage is required for normal in vivo oligodendrocyte development and myelination
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DOI：
10.1002/glia.20469
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发表时间：
2007-03
期刊：
影响因子：
6.2
通讯作者：
M. Zeger;Gregory J. Popken;Jihui Zhang;S. Xuan;Q. Lu;M. Schwab;K. Nave;D. Rowitch;A. D'ercole;P. Ye
中科院分区：
文献类型：
--
作者：
M. Zeger;Gregory J. Popken;Jihui Zhang;S. Xuan;Q. Lu;M. Schwab;K. Nave;D. Rowitch;A. D'ercole;P. Ye
胰岛素样生长因子-I（IGF-I）已被证明是促进少突胶质细胞前体生长和分化以及在发育期间和损伤后刺激髓鞘形成的有效药物。为了明确确定IGF-I是否直接作用于少突胶质细胞谱系的细胞，我们产生了小鼠系，其中在Olig 1或蛋白脂质蛋白表达细胞中的1型IGF受体基因（igf 1 r）被条件性消融（分别称为IGF 1 Rpre ‐oligo‐ko和IGF 1 Roligo ‐ko小鼠）。与野生型小鼠相比，IGF 1 Rpre ‐oligo‐ko小鼠在2周龄和6周龄时胼胝体（CC）和前连合中的体积和细胞数量分别减少（35-55%）和54-70%。25周龄的IGF 1 Roligo-ko小鼠也显示出CC体积和细胞数量的减少，尽管不太明显。与星形胶质细胞不同，NG 2+少突胶质细胞前体的百分比在2周龄IGF 1 Rpre ‐oligo‐ko小鼠中降低了13%，而CC 1+成熟少突胶质细胞的百分比在6周龄IGF 1 Rpre ‐oligo‐ko小鼠中降低了124%，在25周龄IGF 1 Roligo ‐ko小鼠中降低了125%。这些细胞的减少显然是增殖减少和凋亡增加的结果。这些结果表明，IGF-I通过IGF 1 R直接影响体内少突胶质细胞和髓鞘形成，并且少突胶质细胞谱系细胞中的IGF 1 R信号传导是正常少突胶质细胞发育和髓鞘形成所必需的。这些数据还为开发具有靶向少突胶质细胞谱系细胞中的IGF-IGF 1 R信号通路以治疗脱髓鞘疾病的潜力的策略提供了基本基础。© 2006 Wiley利斯公司
Insulin‐like growth factor‐I (IGF‐I) has been shown to be a potent agent in promoting the growth and differentiation of oligodendrocyte precursors, and in stimulating myelination during development and following injury. To definitively determine whether IGF‐I acts directly on the cells of oligodendrocyte lineage, we generated lines of mice in which the type 1 IGF receptor gene (igf1r) was conditionally ablated either in Olig1 or proteolipid protein expressing cells (termed IGF1Rpre‐oligo‐ko and IGF1Roligo‐ko mice, respectively). Compared with wild type mice, IGF1Rpre‐oligo‐ko mice had a decreased volume (by 35–55%) and cell number (by 54–70%) in the corpus callosum (CC) and anterior commissure at 2 and 6 weeks of age, respectively. IGF1Roligo‐ko mice by 25 weeks of age also showed reductions, albeit less marked, in CC volume and cell number. Unlike astrocytes, the percentage of NG2+ oligodendrocyte precursors was decreased by ∼13% in 2‐week‐old IGF1Rpre‐oligo‐ko mice, while the percentage of CC1+ mature oligodendrocytes was decreased by ∼24% in 6‐week‐old IGF1Rpre‐oligo‐ko mice and ∼25% in 25‐week‐old IGF1Roligo‐ko mice. The reduction in these cells is apparently a result of decreased proliferation and increased apoptosis. These results indicate that IGF‐I directly affects oligodendrocytes and myelination in vivo via IGF1R, and that IGF1R signaling in the cells of oligodendrocyte lineage is required for normal oligodendrocyte development and myelination. These data also provide a fundamental basis for developing strategies with the potential to target IGF‐IGF1R signaling pathways in oligodendrocyte lineage cells for the treatment of demyelinating disorders. © 2006 Wiley‐Liss, Inc.