Soares S, Fischer I, Ravaille-Veron M, Vincent J D, Nothias F
Institut Alfred Fessard, Gif-Sur Yvette, France.
J Comp Neurol. 1998 Jun 29;396(2):193-210.
We have previously shown that the phosphorylated form of microtubule-associated protein 1B (MAP1B-P), which is located in growing axons during development and regeneration, remains detectable in the adult central nervous system only in areas that undergo morphologic plasticity (Nothias et al. [1996] J. Comp. Neurol. 368:317-334). Our objective in the present study was to determine whether lesion-induced axonal remodeling, in the adult rat, is associated with reinduction of MAP1B phosphorylation. MAP1B-P was not detectable in intact adult thalamic ventrobasal complex (VB), although low levels of MAP1B and its mRNA were present. A neuron-depletion of VB by in situ injection of kainic acid was followed by an induction of MAP1B phosphorylation by 24 hours postlesion. MAP1B-P was detected in fibers originating from undamaged neurons that were not located in the lesion, as demonstrated by the absence of hybridized MAP1B-mRNA. Ultrastructural analysis confirmed the exclusive location of MAP1B-P in axons in a proximodistal gradient. MAP1B phosphorylation appeared to be regulated by posttranslational modification of existing protein because the levels of MAP1B-mRNA did not change. The number of MAP1B-P-labeled fibers increased during the first month postlesion and remained high for a long period. Double staining by using axonal tracing with dextran-biotin and tyrosine hydroxylase immunohistochemistry, showed the presence of MAP1B-P in VB afferents from somatosensory relays and the locus coeruleus. This study supports the hypothesis that MAP1B, at a particular state of phosphorylation, is correlated with axonal remodeling in the adult central nervous system (CNS). We suggest that the interaction of MAP1B-P with microtubules allows the modulation of their dynamic properties during periods of increased axonal plasticity.
我们之前已经表明，微管相关蛋白1B的磷酸化形式（MAP1B-P）在发育和再生过程中位于生长的轴突中，仅在经历形态可塑性的成年中枢神经系统区域中仍可检测到（诺蒂亚斯等人[1996年]《比较神经学杂志》368:317 - 334）。我们在本研究中的目的是确定成年大鼠中损伤诱导的轴突重塑是否与MAP1B磷酸化的重新诱导相关。在完整的成年丘脑腹侧基底复合体（VB）中未检测到MAP1B-P，尽管存在低水平的MAP1B及其mRNA。通过原位注射 kainic 酸使VB中的神经元耗竭后，在损伤后24小时诱导了MAP1B磷酸化。如未杂交的MAP1B-mRNA所示，在源自未受损神经元且不在损伤部位的纤维中检测到了MAP1B-P。超微结构分析证实了MAP1B-P在轴突中以近端到远端的梯度存在。由于MAP1B-mRNA的水平没有变化，MAP1B磷酸化似乎受现有蛋白质的翻译后修饰调节。损伤后第一个月内，MAP1B-P标记的纤维数量增加，并在很长一段时间内保持高水平。使用右旋糖酐生物素进行轴突追踪和酪氨酸羟化酶免疫组织化学的双重染色显示，在来自体感中继和蓝斑的VB传入纤维中存在MAP1B-P。本研究支持以下假设：处于特定磷酸化状态的MAP1B与成年中枢神经系统（CNS）中的轴突重塑相关。我们认为，MAP1B-P与微管的相互作用允许在轴突可塑性增加的时期调节其动态特性。
