Department of Psychiatry, Washington University, St. Louis, MO 63110-1093, USA.
Neurobiol Dis. 2010 Oct;40(1):200-6. doi: 10.1016/j.nbd.2010.05.025. Epub 2010 May 23.
The ability of brief exposure to alcohol to cause widespread neuroapoptosis in the developing rodent brain and subsequent long-term neurocognitive deficits has been proposed as a mechanism underlying the neurobehavioral deficits seen in fetal alcohol spectrum disorder (FASD). It is unknown whether brief exposure to alcohol causes apoptosis in the fetal primate brain. Pregnant fascicularis macaques at various stages of gestation (G105 to G155) were exposed to alcohol for 8h, then the fetuses were delivered by caesarean section and their brains perfused with fixative and evaluated for apoptosis. Compared to saline control brains, the ethanol-exposed brains displayed a pattern of neuroapoptosis that was widespread and similar to that caused by alcohol in infant rodent brain. The observed increase in apoptosis was on the order of 60-fold. We propose that the apoptogenic action of alcohol could explain many of the neuropathological changes and long-term neuropsychiatric disturbances associated with human FASD.
短暂暴露于酒精会导致发育中啮齿动物大脑广泛的神经细胞凋亡,并随后出现长期的神经认知缺陷,这被认为是胎儿酒精谱系障碍(FASD)中所见的神经行为缺陷的一种机制。目前尚不清楚短暂暴露于酒精是否会导致胎儿灵长类动物大脑发生细胞凋亡。处于不同妊娠阶段(G105 至 G155)的食蟹猕猴被暴露于酒精中 8 小时,然后通过剖腹产分娩胎儿,并对其大脑进行灌注固定,以评估细胞凋亡情况。与生理盐水对照大脑相比,乙醇暴露的大脑显示出广泛的神经细胞凋亡模式,类似于酒精在婴儿啮齿动物大脑中引起的模式。观察到的细胞凋亡增加约为 60 倍。我们提出,酒精的促凋亡作用可以解释许多与人类 FASD 相关的神经病理学变化和长期神经精神障碍。