Terao E, Janssens S, van den Bosch de Aguilar P, Portier M, Klosen P
Laboratoire de Biologie Cellulaire, Université Catholique de Louvain, 5 Place Croix du Sud, B-1348, Louvain-la-Neuve, Belgium.
Neuroscience. 2000;101(3):679-88. doi: 10.1016/s0306-4522(00)00423-1.
Peripherin is a type III intermediate filament which, in contrast to the neurofilaments, is strongly up-regulated after nerve injury. Although peripherin expression is stimulated in vitro by neurotrophins and cytokines, little is known about its in vivo regulation. In this report, we show that the in vivo down-regulation of peripherin expression to normal levels during regeneration closely correlates with target reconnection in rat facial motoneurons. Prevention of reconnection, by transection and suture, results in the persistence of strong peripherin expression for prolonged periods of up to 11months. This contrasts with the modulation of the p75 low-affinity neurotrophin receptor, whose expression returns to normal even in the absence of reconnection. We further demonstrate that blockade of the axonal transport in non-injured motoneurons increases the expression of peripherin. Blockade of the axonal transport simultaneously to, or after injury of, facial motoneurons does not abolish the axotomy-induced peripherin up-regulation. These data demonstrate that the in vivo expression of peripherin is normally restrained by a distal retrogradely transported inhibitory signal. Thus, peripherin up-regulation results primarily from a lack of supply in this factor. Our results show that stimulatory factors released at the injury site are not required for the initial up-regulation and maintenance of high peripherin expression. However, they appear to enhance this increase during the acute post-lesion phase. Peripherin expression is thus finely tuned by both glial cell-derived stimulatory and distal inhibitory signals that reflect neuron-target interactions.
外周蛋白是一种III型中间丝，与神经丝不同，在神经损伤后它会强烈上调表达。尽管神经营养因子和细胞因子在体外可刺激外周蛋白的表达，但对其体内调节机制却知之甚少。在本报告中，我们发现大鼠面部运动神经元再生过程中外周蛋白表达在体内下调至正常水平与靶标重新连接密切相关。通过横断和缝合阻止重新连接，会导致外周蛋白长时间持续强烈表达，长达11个月。这与p75低亲和力神经营养因子受体的调节形成对比，后者即使在没有重新连接的情况下其表达也会恢复正常。我们进一步证明，阻断未损伤运动神经元中的轴突运输会增加外周蛋白的表达。在面部运动神经元损伤的同时或之后阻断轴突运输，并不会消除轴突切断诱导的外周蛋白上调。这些数据表明，外周蛋白在体内的表达通常受到远端逆行运输的抑制信号的限制。因此，外周蛋白上调主要是由于该因子供应不足所致。我们的结果表明，损伤部位释放的刺激因子对于外周蛋白高表达的初始上调和维持并非必需。然而，它们似乎在损伤后急性期增强了这种增加。因此，外周蛋白的表达受到反映神经元-靶标相互作用的胶质细胞衍生的刺激信号和远端抑制信号的精细调节。
