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Brain development retardation in insulin-like growth factor binding protein-1 transgenic mice.

机译：胰岛素样生长因子结合蛋白1转基因小鼠的大脑发育迟缓。

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摘要

In order to determine the effects of IGF-I in brain development in vivo, we studied the brain development of transgenic mice that overexpress rat IGFBP-1 under the control of PGK promoter. The gross morphology of the brain in the transgenic mice was not different from those wild type control mice. Brains from the IGFBP-1 transgenic mice had reduction in weight owning to decreased total brain cell numbers. Retardation of brain growth was observed at the age as early as P0 and thereafter. The markedly reduced corpus callosum thickness in transgenic mice indicates decreased axons due to the expression of transgene. The area of hippocampus and dentate gyrus were reduced in excess of the decrease in brain weight. The distribution of cholinergic neurons, astroglia and microglia were not affected by transgene expression. The cell proliferation study showed reduced proliferating brain cells in the ventricular zone (VZ), the subventricular zone (SVZ) and the developing hippocampus, and increased apoptotic cells in neonatal transgenic mice. To further examine cell proliferation in transgenic mice, we introduced a stab wound to induce a brain lesion in adult transgenic mice and wild type control. The number of reactive astroglia was significantly reduced in transgenic mice, the immunostaining intensity for glial fibrillary acidic protein (GFAP) was also decreased in transgenic mice. These data demonstrate that the overexpression of IGFBP-1 via its inhibitory effect on IGF-I action selectively inhibit brain development. Our findings also suggest an in vivo promoting role of IGF-I on brain response to injury.
机译：为了确定IGF-I在体内大脑发育中的作用，我们研究了在PGK启动子控制下过表达大鼠IGFBP-1的转基因小鼠的大脑发育。转基因小鼠的大脑总体形态与野生型对照小鼠没有什么不同。由于总脑细胞数量减少，IGFBP-1转基因小鼠的大脑体重减轻。早在P0以及此后的年龄就观察到大脑发育的迟缓。转基因小鼠的call体厚度显着减少，这表明由于转基因的表达，轴突减少。海马和齿状回的面积减少超过了脑重量的减少。胆碱能神经元，星形胶质细胞和小胶质细胞的分布不受转基因表达的影响。细胞增殖研究表明，新生转基因小鼠脑室区（VZ），脑室下区（SVZ）和发育中的海马中增殖的脑细胞减少，凋亡细胞增多。为了进一步检查转基因小鼠中的细胞增殖，我们引入了刺伤，以在成年转基因小鼠和野生型对照中诱发脑损伤。转基因小鼠的活动性星形胶质细胞数目明显减少，转基因小鼠的神经胶质纤维酸性蛋白（GFAP）的免疫染色强度也降低。这些数据表明，IGFBP-1通过其对IGF-I作用的抑制作用而过表达选择性地抑制了大脑发育。我们的发现还暗示了IGF-I在脑损伤反应中的体内促进作用。

著录项

  • 作者

    Ni, Weimin.;

  • 作者单位

    University of Manitoba (Canada).;

  • 授予单位 University of Manitoba (Canada).;
  • 学科 Biology Neuroscience.; Health Sciences Mental Health.; Health Sciences Medicine and Surgery.
  • 学位 M.Sc.
  • 年度 1997
  • 页码 94 p.
  • 总页数 94
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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