Tang J, Landmesser L
Department of Physiology and Neurobiology, University of Connecticut, Storrs 06269-3042.
J Neurosci. 1993 Jul;13(7):3095-103. doi: 10.1523/JNEUROSCI.13-07-03095.1993.
Blockade of neuromuscular activity during the period of naturally occurring cell death increases intramuscular nerve branching, synaptogenesis, and survival of embryonic chicken motoneurons. These results suggested that the enhanced motoneuron survival observed might result not from increased production of a trophic factor by the target, as often suggested, but rather from the enhanced ability of motoneurons to take up this factor via additional branches and/or synapses. Since removal of polysialic acid (PSA) by PSA-specific endoneuraminidase (endo N) during the period of nerve ingrowth and motoneuron cell death had been shown to reduce intramuscular nerve branching by altering adhesive interactions between axons and myotubes, we wished to determine, first, if this resulted in a reduction of synapse formation, and second, if this was correlated with decreased motoneuron survival. When PSA was removed from embryonic day 6 (E6) to E9 by injecting endo N into the limb, the number of synapses in the posterior iliotibialis muscle was greatly reduced both at E6.5, the onset of the cell death period, and at E7.5-E8, the middle of the cell death period. Total motoneuron counts at both E7.5-E8 and E10 (close to the end of cell death period) were significantly decreased compared to controls. These results indicate that a treatment that reduces intramuscular nerve branching and synapse formation also affects motoneuron survival. Furthermore, since removal of PSA in ovo via endo N altered neither the spontaneous embryonic motility nor the activation pattern of motoneurons or muscles, these experiments avoid the complication of activity blockade that may alter motoneuron survival by affecting events other than, or in addition to, intramuscular nerve branching.
在自然发生细胞死亡的时期阻断神经肌肉活动，会增加胚胎鸡运动神经元的肌内神经分支、突触形成和存活。这些结果表明，观察到的运动神经元存活率提高，可能并非如通常所认为的那样，是由于靶标产生的营养因子增加，而是由于运动神经元通过额外的分支和/或突触摄取该因子的能力增强。由于在神经长入和运动神经元细胞死亡期间，用多唾液酸（PSA）特异性内切神经氨酸酶（内切N）去除PSA已被证明会通过改变轴突与肌管之间的黏附相互作用来减少肌内神经分支，我们首先想确定这是否会导致突触形成减少，其次确定这是否与运动神经元存活率降低相关。通过向肢体注射内切N从胚胎第6天（E6）到E9去除PSA时，在细胞死亡期开始的E6.5以及细胞死亡期中期的E7.5 - E8，髂胫后肌中的突触数量均大幅减少。与对照组相比，在E7.5 - E8和E10（接近细胞死亡期结束）时的运动神经元总数均显著减少。这些结果表明，减少肌内神经分支和突触形成的处理也会影响运动神经元的存活。此外，由于通过内切N在卵内去除PSA既未改变胚胎的自发运动，也未改变运动神经元或肌肉的激活模式，这些实验避免了活动阻断带来的复杂性，活动阻断可能会通过影响除肌内神经分支之外或与之相关的其他事件来改变运动神经元的存活。
