Soares Sylvia, Barnat Monia, Salim Claudio, von Boxberg Ysander, Ravaille-Veron Michèle, Nothias Fatiha
Université Pierre et Marie Curie-Paris6, UMR7101 NSI, Paris, F-75005 France,
Eur J Neurosci. 2007 Sep;26(6):1446-61. doi: 10.1111/j.1460-9568.2007.05794.x.
Spinal cord injury (SCI) results in loss of sensory and motor function because injured axons do not regenerate and neurons that die are not replaced. Nevertheless, there is evidence for spontaneous reorganization of spared pathways (i.e. sprouting) that could be exploited to improve functional recovery. The extent of morphological remodeling after spinal cord injury is, however, not understood. We have previously shown that a phosphorylated form of microtubule-associated protein-1B, MAP1B-P, is expressed by growing axons, but is detected in intact adult SC in fibers exhibiting a somatotopic distribution of myelinated sensory fibers. We now demonstrate that after adult SCI, MAP1B-P is up-regulated in other classes of axons. We used immunohistochemistry to show changing levels and distributions of MAP1B-P after a right thoracic hemisection of adult rat spinal cord. MAP1B-P labeling suggests rearrangements of the axonal circuitry that go well beyond previous descriptions. MAP1B-P-positive fibers are present in ectopic locations in gray matter in both dorsal and ventral horns and around the central canal. Double staining reveals that primary sensory and descending serotonergic and corticospinal axons are MAP1B-P positive. In white matter, high MAP1B-P expression is found on terminal enlargements near the injury, reflecting retraction of transected axons. MAP1B-P also accumulates in pre-apoptotic neuronal somata axotomized by the lesion, indicating association of MAP1B-P not only with axon extension and retraction, but also with neuronal degeneration. Finally, we provide evidence that MAP1B phosphorylation is correlated with activation of JNK MAP-kinase, providing a step towards unraveling the mechanisms of regulation of this plasticity-related cytoskeletal protein.
脊髓损伤（SCI）会导致感觉和运动功能丧失，因为受损的轴突无法再生，死亡的神经元也无法替代。然而，有证据表明 spared 通路会自发重组（即发芽），这可被利用来促进功能恢复。然而，脊髓损伤后形态重塑的程度尚不清楚。我们之前已经表明，微管相关蛋白 -1B 的磷酸化形式，即 MAP1B-P，由生长中的轴突表达，但在完整成年脊髓中，在呈现髓鞘化感觉纤维躯体定位分布的纤维中也能检测到。我们现在证明，成年脊髓损伤后，MAP1B-P 在其他类型的轴突中上调。我们使用免疫组织化学方法来显示成年大鼠脊髓右侧胸段半切术后 MAP1B-P 的水平和分布变化。MAP1B-P 标记表明轴突回路的重排比之前描述的要广泛得多。MAP1B-P 阳性纤维存在于背角和腹角灰质以及中央管周围的异位位置。双重染色显示，初级感觉轴突以及下行的血清素能和皮质脊髓轴突都是 MAP1B-P 阳性。在白质中，损伤附近的终末膨大处发现高 MAP1B-P 表达，反映了横断轴突的回缩。MAP1B-P 也在因损伤而轴突切断的凋亡前神经元胞体中积累，表明 MAP1B-P 不仅与轴突延伸和回缩有关，还与神经元变性有关。最后，我们提供证据表明 MAP1B 磷酸化与 JNK 丝裂原活化蛋白激酶的激活相关，这为揭示这种与可塑性相关的细胞骨架蛋白的调节机制迈出了一步。
