Schenker Michel, Riederer Beat Michel, Kuntzer Thierry, Barakat-Walter Ibtissam
Institute of Cell Biology and Morphology (IBCM), Medical School, Lausanne, Switzerland.
Brain Res. 2002 Dec 13;957(2):259-70. doi: 10.1016/s0006-8993(02)03607-7.
Peripheral neurons can regenerate after axotomy; in this process, the role of cytoskeletal proteins is important because they contribute to formation and reorganization, growth, transport, stability and plasticity of axons. In the present study, we examined the effects of thyroid hormones (T3) on the expression of major cytoskeletal proteins during sciatic nerve regeneration. At various times after sciatic nerve transection and T3 local administration, segments of operated nerves from T3-treated rats and control rats were examined by Western blotting for the presence of neurofilament, tubulin and vimentin. Our results revealed that, during the first week after surgery, T3 treatment did not significantly alter the level of NF subunits and tubulin in the different segments of operated nerves compared to control nerves. Two or 4 weeks after operation, the concentration of NF-H and NF-M isoforms was clearly increased by T3 treatment. Moreover, under T3-treatment, NF proteins appeared more rapidly in the distal segment of operated nerves. Likewise, the levels of betaIII, and of acetylated and tyrosinated tubulin isotypes, were also up-regulated by T3-treatment during regeneration. However, only the tyrosinated tubulin form appeared earlier in the distal nerve segments. At this stage of regeneration, T3 had no effect on the level of vimentin expression. In conclusion, thyroid hormone improves and accelerates peripheral nerve regeneration and exerts a positive effect on cytoskeletal protein expression and transport involved in axonal regeneration. These results help us to understand partially the mechanism by which thyroid hormones enhance peripheral nerve regeneration. The stimulating effect of T3 on peripheral nerve regeneration may have considerable therapeutic potential.
外周神经元在轴突切断后能够再生；在此过程中，细胞骨架蛋白的作用至关重要，因为它们有助于轴突的形成、重组、生长、运输、稳定性和可塑性。在本研究中，我们检测了甲状腺激素（T3）对坐骨神经再生过程中主要细胞骨架蛋白表达的影响。在坐骨神经横断并局部给予T3后的不同时间点，通过蛋白质免疫印迹法检测T3处理组大鼠和对照组大鼠手术神经段中神经丝、微管蛋白和波形蛋白的表达情况。我们的结果显示，在手术后的第一周，与对照神经相比，T3处理并未显著改变手术神经不同节段中NF亚基和微管蛋白的水平。术后2周或4周，T3处理明显增加了NF-H和NF-M亚型的浓度。此外，在T3处理下，NF蛋白在手术神经的远端节段出现得更快。同样，在再生过程中，T3处理也上调了βIII、乙酰化和酪氨酸化微管蛋白亚型的水平。然而，只有酪氨酸化微管蛋白形式在远端神经节段中出现得更早。在这个再生阶段，T3对波形蛋白的表达水平没有影响。总之，甲状腺激素可改善并加速外周神经再生，并对轴突再生过程中涉及的细胞骨架蛋白表达和运输产生积极影响。这些结果有助于我们部分理解甲状腺激素增强外周神经再生的机制。T3对外周神经再生的刺激作用可能具有相当大的治疗潜力。
