Shi B, Stanfield B B
Laboratory of Neurophysiology, National Institute of Mental Health, NIH Animal Center, Poolesville, MD 20837, USA.
Brain Res. 1996 Nov 18;740(1-2):89-101. doi: 10.1016/s0006-8993(96)00849-9.
Axons in both peripheral nerves and central fiber pathways undergo very slow Wallerian degeneration in Wlds mutant mice. It has recently been shown that in Wlds mutant mice there is a delay in the intensification of acetylcholinesterase histochemical staining in the molecular layer of the dentate gyrus following lesions of the entorhinal cortex. Thus, it appears that delayed post-lesion reactive sprouting is associated with the delayed degeneration of cut central axons in this mutant. We have studied the time course of changes in the septohippocampal and the hippocampal commissural projections following interruption of perforant path in Wlds mutant mice and in normal (C57BL/6J) mice using the anterograde tracer, wheat germ agglutinin conjugated horseradish peroxidase. In normal mice, changes in the distribution of labeled septal and commissural axons indicative of sprouting are seen in the dentate molecular layer as early as 3 days post-lesion. The earliest survival time at which similar changes are found in Wlds mutant mice is seven days post-lesion, when an increase in the density of labeled septal axons begins in the outer molecular layer. The delay in the sprouting of commissural axons in the mutant is even longer. Changes in the distribution of labeled commissural axons in the dentate gyrus of Wlds mutant mice are first seen 12 days post-lesion. These results confirm that post-lesion reactive axonal sprouting can be delayed in the central nervous system of Wlds mutant mice. In addition, our results indicate that the extent of this delay may differ among axonal fiber systems. These findings are consistent with the notion that various central axonal systems may respond differentially to sprouting cues and are reminiscent of differences found in the regenerating response exhibited by sensory and motor axons in the Wlds mutant after peripheral nerve cuts.
在Wlds突变小鼠中，外周神经和中枢纤维通路中的轴突都会发生非常缓慢的沃勒变性。最近有研究表明，在Wlds突变小鼠中，内嗅皮质损伤后，齿状回分子层中乙酰胆碱酯酶组织化学染色的强化出现延迟。因此，在这种突变体中，损伤后反应性发芽延迟似乎与切断的中枢轴突的延迟变性有关。我们使用顺行示踪剂——小麦胚凝集素结合辣根过氧化物酶，研究了Wlds突变小鼠和正常（C57BL/6J）小鼠在穿通通路中断后，隔海马和海马连合投射的变化时间进程。在正常小鼠中，早在损伤后3天，在齿状分子层中就可以看到标记的隔区和连合轴突分布的变化，这表明有发芽现象。在Wlds突变小鼠中最早发现类似变化的存活时间是损伤后7天，此时标记的隔区轴突密度在外分子层开始增加。突变体中连合轴突发芽的延迟甚至更长。在Wlds突变小鼠齿状回中标记的连合轴突分布的变化在损伤后12天首次出现。这些结果证实，在Wlds突变小鼠的中枢神经系统中，损伤后反应性轴突发芽可能会延迟。此外，我们的结果表明，这种延迟的程度在不同的轴突纤维系统中可能有所不同。这些发现与各种中枢轴突系统可能对发芽信号有不同反应的观点一致，并且让人想起在Wlds突变体中，外周神经切断后感觉和运动轴突在再生反应中发现的差异。
