Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats
Delayed changes in growth factor gene expression during slow remyelination in the CNS of aged rats
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DOI：
10.1006/mcne.2000.0897
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发表时间：
2000-11-01
影响因子：
3.5
通讯作者：
Franklin, RJM
中科院分区：
文献类型：
--
作者：
Hinks, GL;Franklin, RJM
在这项研究中，我们研究了是否与生长因子表达模式的变化，生长因子和髓鞘再生之间的因果关系提供了进一步的支持，生长因子和髓鞘再生的速度较慢，发生与年龄相关。使用定量原位杂交，我们已经表明，有差异的IGF-I，TGF-β 1，和PDGF-A的mRNA表达在髓鞘再生的溶血卵磷脂诱导的脱髓鞘在年轻的成年和老年成年大鼠的脊髓。IGF-I和TGF-β 1 mRNA在老年大鼠中的表达与年轻大鼠相比具有延迟和较低的峰值表达。与年轻大鼠相比，老年大鼠PDGF-A mRNA表达的初始增加延迟，但5天后，两个年龄组的表达模式相似，在所有生存时间内FGF-P mRNA的表达模式也相似。在这两个年龄组的CNTF，NT-3，或GGF-2 mRNA表达的增加检测。使用清道夫受体-α mRNA的寡核苷酸探针对巨噬细胞反应的分析表明，年轻和年老动物中巨噬细胞反应的差异可能是IGF-I和TGF-β 1 mRNA表达模式中年龄相关变化的原因。在这些数据的基础上，我们提出了一种髓鞘再生模型，其中PDGF参与了少突胶质细胞祖细胞招募的初始阶段，而IGF-I和TGF-β 1触发了招募的细胞分化成髓鞘少突胶质细胞。
In this study we have examined whether the slower rate of CNS remyelination that occurs with age is associated with a change in growth factor expression patterns, an association that would provide further support for a causal relationship between growth factors and remyelination. Using quantitative in situ hybridization we have shown that there are differences in IGF-I, TGF-beta1, and PDGF-A mRNA expression during remyelination of lysolecithin-induced demyelination in the spinal cord of young adult and old adult rats. IGF-I and TGF-beta1 mRNA expression in old rats had a delayed and lower peak expression compared to young rats. The initial increase in PDGF-A mRNA expression was delayed in old rats compared to young rats, but after 5 days both age groups had similar patterns of expression, as was the expression pattern of FGF-P mRNA at all survival times. In neither age group were increases in CNTF, NT-3, or GGF-2 mRNA expression detected. An analysis of the macrophage response using oligonucleotide probes for scavenger receptor-a mRNA indicated that differences in the macrophage response in young and old animals was the likely cause of the age related change in IGF-I and TGF-beta1 mRNA expression patterns. On the basis of these data we suggest a model of remyelination in which PDGF is involved in the initial phase of oligodendrocyte progenitor recruitment, while IGF-I and TGF-beta1 trigger the differentiation of the recruited cells into myelinating oligodendrocytes.