Clarification of roles of gangliosides in nerve regeneration using mice lacking complex gangliosides

为了阐明神经节苷脂在包括神经再生在内的神经功能中的作用和机制，对缺乏复杂神经节苷脂的小鼠进行了体内和体外研究。在体内实验中，对N-乙酰氨基半乳糖胺转移酶基因敲除(GalNacT-/-)小鼠的坐骨神经损伤进行电生理检测，并与野生型小鼠进行比较；挤压后4天的收缩反射试验显示，两组小鼠的再生长度无差异。神经传导检测显示，坐骨神经损伤前和损伤后7周，坐骨神经-胫神经复合肌肉动作电位和末端潜伏期组间差异无统计学意义。在体外实验中，MAG-Fc不与GalNacT-/-小鼠小脑颗粒细胞结合，而与GD3合成酶-/-小鼠小脑颗粒细胞部分结合，与WIL型小鼠小脑颗粒细胞结合良好。此外，这些结合与神经细丝染色评估的轴突延伸的大小平行。鉴于GalNacT-/-小鼠没有MAG的潜在配体GT1b或GD1a，而GD3合成酶-/-小鼠有少量的MAG配体，这些结果表明神经节苷脂可能在神经粘连或再生中发挥重要作用。

To clarify either the roles or mechanisms of gangliosides in nerve function including nerve regerneration, in vivo and in vitro studies were undertaken using mice lacking complex gangliosides. In in vivo study crushed sciatic nerves of N-acetylgalctosamine-transferase knockout (GalNacT-/-) mice were electrophysiologically evaluated and compared with wild-type mice at intervals after crush ; pinch reflex test 4 days after crush showed no difference in regeneration length between groups. In addition, nerve conduction study also showed no difference in compound muscle action potential and terminal latency of sciatic-tibial nerve before and up to 7 weeks after nerve crush between groups. In vitro study, MAG-Fc did not bind to cerebellar granular cells from GalNacT-/-mice, but partially bound to those from GD3 synthase-/-mice and well bound to those from wil type mice. Furthermore, those binding paralleled with the magnitude of neurite extension evaluated by staining of neurofilaments. In view of the fact that GalNacT-/- mice do not have GT1b or GD1a, potential ligand for MAG and GD3 synthase -/-mice have a small amount of MAG ligands, these results suggest that gangliosides may play an important role in nerve adhesion or regeneration.