Parson S H, Sojitra N M
Department of Anatomy, University Medical School, Edinburgh, UK.
J Anat. 1995 Dec;187 ( Pt 3)(Pt 3):739-48.
We have previously developed a mouse model of the fetal alcohol syndrome, the outcome of which is a late loss of myelinated axons in the optic nerve of offspring of alcohol-treated mice between 9 and 15 wk of age. We have extended this study to investigate whether this axon loss is stable and specific to the central nervous system. Pregnant female (C57BL/6/Wlds x CBA) F1 mice were injected intraperitoneally with a single dose of a 25% solution of ethanol (v:w), on d 12 of gestation. Control animals were given a similar volume of saline at the same time. Litters were taken at 12 (n = 18) and 23 (n = 26) wk of age. Optic nerves only from 12-wk-old, and optic, tibial and saphenous nerves from 23-wk-old mice were removed. A systematic, random sampling method was used to estimate the cross-sectional area of whole nerves from semi thin sections, and the numbers and diameters of myelinated axons from ultrathin sections. There were no differences for the optic nerves of 12-wk-old alcohol-treated and control animals. Optic nerves from the alcohol-treated group at 23 wk had smaller cross-sectional areas and approximately 17% fewer myelinated axons than control nerves. These results confirm that axon loss occurs between 12 and 15 wk, and demonstrate that there is no additional loss of myelinated axons between 15 and 23 wk. In contrast, there were no significant differences in cross-sectional area, number of myelinated axons or axon calibre spectra for the tibial and saphenous nerves between the alcohol-treated and control groups. There was thus no evidence of a peripheral neuropathy as has been observed in chronic alcoholic subjects. In this 'binge' model of the fetal alcohol syndrome, a carefully timed dose of alcohol is administered during pregnancy to coincide with a critical period of development of the visual system. The result is a teratogenic effect which is specific to the central nervous system, stable and reproducible, with no obvious effect on the peripheral nervous system.
我们之前建立了一种胎儿酒精综合征的小鼠模型，其结果是，在9至15周龄时，经酒精处理的小鼠后代的视神经中，有髓轴突出现晚期丢失。我们扩展了这项研究，以调查这种轴突丢失是否稳定且是否特定于中枢神经系统。怀孕的雌性（C57BL/6/Wlds×CBA）F1小鼠在妊娠第12天腹腔注射单剂量25%（体积比）的乙醇溶液。对照组动物在同一时间给予相同体积的生理盐水。在12周龄（n = 18）和23周龄（n = 26）时取仔鼠。仅从12周龄小鼠身上取出视神经，从23周龄小鼠身上取出视神经、胫神经和隐神经。采用系统随机抽样方法，从半薄切片估计全神经的横截面积，从超薄切片估计有髓轴突的数量和直径。12周龄经酒精处理的动物和对照动物的视神经没有差异。23周龄时，经酒精处理组的视神经横截面积较小，有髓轴突比对照神经少约17%。这些结果证实轴突丢失发生在12至15周之间，并表明在15至23周之间没有额外的有髓轴突丢失。相比之下，经酒精处理组和对照组的胫神经和隐神经在横截面积、有髓轴突数量或轴突管径谱方面没有显著差异。因此，没有证据表明存在慢性酒精中毒患者中所观察到的周围神经病变。在这种胎儿酒精综合征的“暴饮”模型中，在孕期适时给予一剂酒精，使其与视觉系统发育的关键时期相吻合。结果是产生了一种特定于中枢神经系统的致畸效应，这种效应稳定且可重复，对周围神经系统没有明显影响。
