Busciglio J, Yankner B A
Department of Neurology, Harvard Medical School, Children's Hospital, Boston, Massachusetts 02115, USA.
Nature. 1995;378(6559):776-9. doi: 10.1038/378776a0.
Down's syndrome (DS) or trisomy 21 is the most common genetic cause of mental retardation. Development of the DS brain is associated with decreased neuronal number and abnormal neuronal differentiation, and adults with DS develop Alzheimer's disease. The cause of the neurodegenerative process in DS is unknown. Here we report that cortical neurons from fetal DS and age-matched normal brain differentiate normally in culture, but DS neurons subsequently degenerate and undergo apoptosis whereas normal neurons remain viable. Degeneration of DS neurons is prevented by treatment with free-radical scavengers or catalase. Furthermore, DS neurons exhibit a three- to fourfold increase in intracellular reactive oxygen species and elevated levels of lipid peroxidation that precede neuronal death. These results suggest that DS neurons have a defect in the metabolism of reactive oxygen species that causes neuronal apoptosis. This defect may contribute to mental retardation early in life and predispose to Alzheimer's disease in adults.
唐氏综合征（DS）或21三体综合征是智力发育迟缓最常见的遗传病因。DS患者大脑的发育与神经元数量减少及神经元分化异常有关，成年DS患者会患上阿尔茨海默病。DS神经退行性变过程的病因尚不清楚。在此我们报告，来自唐氏综合征胎儿和年龄匹配正常胎儿大脑的皮质神经元在培养中正常分化，但DS神经元随后会退化并发生凋亡，而正常神经元仍保持存活。用自由基清除剂或过氧化氢酶处理可防止DS神经元退化。此外，DS神经元在细胞内活性氧增加三到四倍，且脂质过氧化水平升高，这些都先于神经元死亡。这些结果表明，DS神经元在活性氧代谢方面存在缺陷，导致神经元凋亡。这一缺陷可能在生命早期导致智力发育迟缓，并使成年人易患阿尔茨海默病。
