Cannella M S, Oderfeld-Nowak B, Gradkowska M, Skup M, Garofalo L, Cuello A C, Ledeen R W
Department of Neurology, Albert Einstein College of Medicine, Bronx, NY 10461.
Brain Res. 1990 Apr 16;513(2):286-94. doi: 10.1016/0006-8993(90)90469-r.
Exogenously administered gangliosides have been shown to behave as neuronotrophic/neuritogenic agents in a variety of cell culture systems and animal models, but it is not known whether they operate by the same mechanism in vivo and in vitro. To probe this question we have employed two derivatives of GM1 lacking the negative charge: the methyl ester (GM1-CH3) and the NaBH4 reduction product of the latter (GM1-OH) in which the carboxyl group is replaced by a primary alcohol. Both derivatives proved to be as neuritogenic as GM1 in 3 cell culture systems: neuro-2A cels, PC12 cells and explanted dorsal root ganglia. However, GM1-OH proved ineffective when applied to two animal models involving reduction of cholinergic markers in: (a) hippocampus following lesion of the lateral fimbria and (b) nucleus basalis magnocellularis following cortical lesion; GM1-CH3 showed marginal activity in (a) but more in (b), possibly owing to slow hydrolysis to GM1 which was highly active in both animal models. These results indicate the necessity of a negative change on the ganglioside molecule for in vivo but not in vitro activity and point to different mechanisms for the trophic effects of exogenous gangliosides.
外源性给予的神经节苷脂在多种细胞培养系统和动物模型中已被证明具有神经营养/促神经突生长因子的作用，但尚不清楚它们在体内和体外是否通过相同的机制发挥作用。为了探究这个问题，我们使用了两种缺乏负电荷的GM1衍生物：甲酯（GM1-CH3）和后者的NaBH4还原产物（GM1-OH），其中羧基被伯醇取代。在3种细胞培养系统中，这两种衍生物均被证明与GM1一样具有促神经突生长作用：Neuro-2A细胞、PC12细胞和背根神经节外植体。然而，当将GM1-OH应用于两种涉及胆碱能标记物减少的动物模型时，结果显示无效：（a）海马外侧穹窿损伤后；（b）皮质损伤后基底大细胞核。GM1-CH3在（a）中显示出微弱的活性，但在（b）中活性更强，这可能是由于其缓慢水解为GM1，而GM1在这两种动物模型中均具有高度活性。这些结果表明，神经节苷脂分子上的负电荷对于体内活性是必需的，但对于体外活性并非如此，这也表明外源性神经节苷脂的营养作用存在不同的机制。
