Jucker M, D'Amato F, Mondadori C, Mohajeri H, Magyar J, Bartsch U, Schachner M
Department of Neurobiology, Swiss Federal Institute of Technology, Zürich, Switzerland.
Neuroscience. 1996 Dec;75(3):703-15. doi: 10.1016/0306-4522(96)00276-x.
Expression of the neural adhesion molecule L1 and its potential involvement in axonal sprouting were examined in the deafferented rat dentate gyrus. We focused on the dentate gyrus because of its well-defined cytoarchitecture and well-characterized neuronal degeneration and sprouting response following entorhinal cortex lesions. In the molecular layer of the dentate gyrus, a trilaminar staining pattern was observed, with the middle molecular layer exhibiting slightly denser immunolabeling compared to both inner and outer molecular layers. Two to 12 days after a unilateral entorhinal cortex lesion, a progressive loss of L1 immunolabeling was noted in the ipsilateral middle and outer molecular layers, followed by a substantial reappearance of immunostaining 65 days after lesion incidence. The width of the immunostained ipsilateral inner molecular layer revealed a progressive widening and by postlesion day 65 occupied about 50% of the total width of the molecular layer. Immunoelectron microscopy localized L1 to the surface of unmyelinated axons in both normal and deafferented dentate gyrus. In situ hybridization revealed L1 messenger RNA confined to neurons throughout the hippocampal formation, but did not indicate changes in L1 messenger RNA levels in the hippocampus, dentate gyrus, entorhinal cortex or basal forebrain in response to unilateral entorhinal cortex lesions. Changes in L1 immunolabeling in the deafferented dentate gyrus corresponded in a spatial and temporal manner to changes of the synaptic marker synaptophysin and axonal marker phosphorylated tau. Results of the present study are most consistent with the view that L1 is expressed on reinnervating fibers after they make synaptic contacts with other structures. Thus, L1 appears to be involved in the maturation and stabilization of reinnervating fibers and consequently may play an important role in the repair process of the lesioned adult CNS.
在去传入神经的大鼠齿状回中检测了神经粘附分子L1的表达及其在轴突发芽中的潜在作用。我们聚焦于齿状回，是因为其细胞结构明确，且在海马旁回损伤后神经元变性和发芽反应的特征明确。在齿状回的分子层中，观察到一种三层染色模式，中间分子层的免疫标记比内、外分子层略密集。单侧海马旁回损伤后2至12天，同侧中间和外分子层的L1免疫标记逐渐减少，随后在损伤发生65天后免疫染色大量重新出现。同侧免疫染色的内分子层宽度逐渐增宽，在损伤后第65天约占分子层总宽度的50%。免疫电子显微镜显示，在正常和去传入神经的齿状回中，L1均定位于无髓轴突表面。原位杂交显示，L1信使核糖核酸局限于整个海马结构的神经元中，但未显示海马、齿状回、海马旁回或基底前脑的L1信使核糖核酸水平因单侧海马旁回损伤而发生变化。去传入神经的齿状回中L1免疫标记的变化在空间和时间上与突触标记物突触素和轴突标记物磷酸化tau的变化相对应。本研究结果最符合以下观点：L1在重新支配的纤维与其他结构形成突触联系后表达于其上。因此，L1似乎参与了重新支配纤维的成熟和稳定，因而可能在成年中枢神经系统损伤的修复过程中发挥重要作用。
