Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice
Increased cell proliferation and granule cell number in the dentate gyrus of protein repair-deficient mice
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DOI：
10.1002/cne.20780
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发表时间：
2005-12-26
影响因子：
2.5
通讯作者：
Houser, CR
中科院分区：
文献类型：
--
作者：
Farrar, CE;Huang, CS;Houser, CR
最近的研究表明，缺乏蛋白质L-异天冬氨酸（D-天冬氨酸）O-甲基转移酶的小鼠（Pcmt 1-/-小鼠）在海马结构以及其他脑区域内的胰岛素样生长因子-I（IGF-I）和胰岛素受体途径发生了改变。然而，这些变化的细胞定位以及这些变化是否可能与增殖区域（如齿状回）内细胞数量的增加有关尚不清楚。在这项研究中，体视学方法被用来证明，这些小鼠有颗粒细胞层和齿状回门的颗粒细胞数量增加。颗粒细胞的数量较高，伴随着大量的细胞进行有丝分裂的齿状回，这表明在成年Pcmt 1- / -小鼠的神经原区神经元细胞增殖的增加。在支持这一点，增加doublecortin标记的未成熟神经元中检测到的齿状回的颗粒下区。此外，双重免疫荧光研究表明，磷酸化的IGF-1/胰岛素受体在颗粒下区定位于未成熟的神经元，这表明增加激活的一个或两个这些受体在Pcmt 1-/-小鼠可能有助于这些细胞的生长和生存。我们建议，在异戊酰蛋白损伤的修复缺陷导致代谢和生长受体途径的改变，这种模式可能是特别相关的神经发生的研究，刺激细胞损伤。
Recent studies have demonstrated that mice lacking protein L-isoaspartate (D-aspartate) O-methyltransferase (Pcmt1-/- mice) have alterations in the insulin-like growth factor-I (IGF-I) and insulin receptor pathways within the hippocampal formation as well as other brain regions. However, the cellular localization of these changes and whether the alterations might be associated with an increase in cell number within proliferative regions, such as the dentate gyrus, were unknown. In this study, stereological methods were used to demonstrate that these mice have an increased number of granule cells in the granule cell layer and hilus of the dentate gyrus. The higher number of granule cells was accompanied by a greater number of cells undergoing mitosis in the dentate gyrus, suggesting that an increase in neuronal cell proliferation occurs in this neurogenic zone of adult Pcmt1- / - mice. In support of this, increased doublecortin labeling of immature neurons was detected in the subgranular zone of the dentate gyrus. In addition, double immunofluorescence studies demonstrated that phosphorylated IGF-1/insulin receptors in the subgranular zone were localized on immature neurons, suggesting that the- increased activation of one or both of these receptors in Pcmt1-/- mice could contribute to the growth and survival of these cells. We propose that deficits in the repair of isoaspartyl protein damage leads to alterations in metabolic and growth-receptor pathways, and that this model may be particularly relevant for studies of neurogenesis that is stimulated by cellular damage.