Dynamic Changes of Neuroskeletal Proteins in DRGs Underlie Impaired Axonal Maturation and Progressive Axonal Degeneration in Type 1 Diabetes
Dynamic Changes of Neuroskeletal Proteins in DRGs Underlie Impaired Axonal Maturation and Progressive Axonal Degeneration in Type 1 Diabetes
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DOI：
10.1155/2009/793281
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发表时间：
2009-01-01
影响因子：
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通讯作者：
Sima, Anders A. F.
中科院分区：
文献类型：
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作者：
Kamiya, Hideki;Zhang, Weixian;Sima, Anders A. F.
我们研究了1型BB/Wor-rats从1周至10个月糖尿病持续时间的进行性轴突功能障碍和结构缺陷的潜在机制。运动和感觉传导速度在糖尿病4周和6周后下降，并在剩余的9个月内进一步下降。有髓腓肠神经纤维在纤维数量和大小上表现出进行性缺陷。2个月时无髓轴突大小的结构缺陷明显，4个月时数量缺陷明显。在这些变化之前，胰岛素、C肽和IGF-1的可用性降低，神经丝和β-III-微管蛋白的表达降低。磷酸化应激激酶如Cdk 5、p-GSK-3 β和p42/44的上调导致神经丝的磷酸化增加。p-GSK-3 β活性的增加与NFH磷酸化的增加相关，而Cdk 5的降低与NFM磷酸化的减少相关。这些数据表明，受损的神经营养支持的结果在顺序受损的合成和翻译后修饰的神经骨骼蛋白，导致轴突功能，成熟和大小进行性赤字。版权所有（C）2009 Hideki Kamiya et al.这是一篇开放获取的文章，根据知识共享署名许可证分发，该许可证允许在任何媒体上无限制地使用，分发和复制，前提是正确引用原始作品。
We investigated mechanisms underlying progressive axonal dysfunction and structural deficits in type 1 BB/Wor-rats from 1 week to 10 month diabetes duration. Motor and sensory conduction velocities were decreased after 4 and 6 weeks of diabetes and declined further over the remaining 9 months. Myelinated sural nerve fibers showed progressive deficits in fiber numbers and sizes. Structural deficits in unmyelinated axonal size were evident at 2 month and deficits in number were present at 4 mo. These changes were preceded by decreased availability of insulin, C-peptide and IGF-1 and decreased expression of neurofilaments and beta-III-tubulin. Upregulation of phosphorylating stress kinases like Cdk5, p-GSK-3 beta, and p42/44 resulted in increased phosphorylation of neurofilaments. Increasing activity of p-GSK-3 beta correlated with increasing phosphorylation of NFH, whereas decreasing Cdk5 correlated with diminishing phosphorylation of NFM. The data suggest that impaired neurotrophic support results in sequentially impaired synthesis and postranslational modifications of neuroskeletal proteins, resulting in progressive deficits in axonal function, maturation and size. Copyright (C) 2009 Hideki Kamiya et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.