Sortwell C E, Daley B F, Pitzer M R, McGuire S O, Sladek J R, Collier T J
Department of Neurological Sciences and Research Center for Brain Repair, Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois 60612, USA.
J Comp Neurol. 2000 Oct 9;426(1):143-53.
Survival of embryonic dopamine (DA) neurons is extremely low (5-20%) following transplantation. Strategies to increase this survival are critical to the future of transplantation for Parkinson's disease. We demonstrate here that a factor(s) released from striatal oligodendrocyte-type 2 astrocytes (SO2A) greatly improves the survival and phenotype expression of mesencephalic DA neurons in culture while simultaneously decreasing the presence of apoptotic nuclear profiles, as detected by the TUNEL method and bisbenzamide/tyrosine hydroxylase double labeling. This SO2A-derived trophic factor(s) has minimal effects on glia and no effect on nondopaminergic mesencephalic neurons. The developmental period during which this SO2A trophic effect occurs (E14-18) coincides with the period when mesencephalic grafts are undergoing the highest rates of apoptosis, i.e., immediately following implantation. Therefore, SO2A-derived trophic factor(s) offers great potential for the augmentation of grafted DA neuron survival.
移植后胚胎多巴胺(DA)神经元的存活率极低(5%-20%)。提高这种存活率的策略对于帕金森病移植的未来至关重要。我们在此证明,纹状体少突胶质细胞2型星形胶质细胞(SO2A)释放的一种或多种因子能显著提高培养中脑DA神经元的存活率和表型表达,同时减少凋亡核形态的出现,这是通过TUNEL法和双苯甲酰胺/酪氨酸羟化酶双重标记检测到的。这种源自SO2A的营养因子对神经胶质细胞影响极小,对非多巴胺能中脑神经元无影响。这种SO2A营养作用发生的发育期(E14-18)与中脑移植物凋亡率最高的时期相吻合,即植入后立即出现凋亡。因此,源自SO2A的营养因子在提高移植DA神经元存活率方面具有巨大潜力。