Sendtner M, Arakawa Y, Stöckli K A, Kreutzberg G W, Thoenen H
Max-Planck Institute for Psychiatry, Planegg-Martinsried, Germany.
J Cell Sci Suppl. 1991;15:103-9. doi: 10.1242/jcs.1991.supplement_15.14.
We have demonstrated that the extensive degeneration of motoneurons in the rat facial nucleus after transection of the facial nerve in newborn rats can be prevented by local ciliary neurotrophic factor (CNTF) administration. CNTF differs distinctly from known neurotrophic molecules such as NGF, BDNF and NT-3 in both its molecular characteristics (CNTF is a cytosolic rather than a secretory molecule) and its broad spectrum of biological activities. CNTF is expressed selectively by Schwann cells and astrocytes of the peripheral and central nervous system, respectively, but not by target tissues of the great variety of CNTF-responsive neurons. CNTF mRNA is not detectable by Northern blot or PCR analysis during embryonic development and immediately after birth. However, during the second post-natal week, a more than 30-fold increase in CNTF mRNA and protein occurs in the sciatic nerve. Since the period of low CNTF levels in peripheral nerves coincides with that of high vulnerability of motoneurons (i.e. axonal lesion results in degeneration of motoneuron cell bodies), insufficient availability of CNTF may be the reason for the rate of lesion-induced cell death of early post-natal motoneurons. Highly enriched embryonic chick motoneurons in culture are supported at survival rates higher than 60% by CNTF, even in single cell cultures, indicating that CNTF acts directly on motoneurons. In contrast to CNTF, the members of the neurotrophin gene family (NGF, BDNF and NT-3) do not support the survival of motoneurons in culture. However, aFGF and bFGF show distinct survival activities which are additive to those of CNTF, resulting in the survival of virtually all motoneurons cultured in the presence of CNTF and bFGF.
我们已经证明，新生大鼠面神经横断后，大鼠面神经核运动神经元的广泛退化可通过局部给予睫状神经营养因子（CNTF）来预防。CNTF在分子特征（CNTF是一种胞质分子而非分泌分子）及其广泛的生物活性方面，与已知的神经营养分子如NGF、BDNF和NT-3明显不同。CNTF分别由外周和中枢神经系统的雪旺细胞和星形胶质细胞选择性表达，但不由多种对CNTF有反应的神经元的靶组织表达。在胚胎发育期间和出生后即刻，通过Northern印迹或PCR分析检测不到CNTF mRNA。然而，在出生后的第二周，坐骨神经中CNTF mRNA和蛋白质增加了30多倍。由于外周神经中CNTF水平较低的时期与运动神经元高易损性时期相吻合（即轴突损伤导致运动神经元细胞体退化），CNTF供应不足可能是出生后早期运动神经元损伤诱导细胞死亡速率的原因。即使在单细胞培养中，培养的高度富集的胚胎鸡运动神经元在CNTF的作用下存活率高于60%，这表明CNTF直接作用于运动神经元。与CNTF相反，神经营养素基因家族的成员（NGF、BDNF和NT-3）在培养中不支持运动神经元的存活。然而，aFGF和bFGF显示出明显的存活活性，这些活性与CNTF的活性相加，导致在存在CNTF和bFGF的情况下培养的几乎所有运动神经元都能存活。
