Phillips D E, Krueger S K, Rydquist J E
Department of Biology, Montana State University, Bozeman 59717-0346.
Int J Dev Neurosci. 1991;9(6):631-47. doi: 10.1016/0736-5748(91)90025-h.
This study evaluated the effects of a combined gestational and 10 day postnatal alcohol exposure (human three trimester equivalency) on the development of myelin and axons in rat optic nerve. Rats were exposed during gestation via liquid diet, then their artificially reared pups were further exposed for 10 postnatal days via an ethanol-containing diet fed by gastrostomy. Control animals from pair-fed dams were artificially reared for 10 days on pair-fed isocaloric diets. Anesthetized animals were perfused with fixative on gestational days (G) 15 and 20 and postnatal days (P) 5, 10, 15, 20, and 90, then optic nerve tissues prepared for electron microscopy. Optic nerve cross-sectional areas were generally less from G20 through P90 in ethanol exposed animals. Counts of the number of myelinated nerve fibers per unit area and of the numbers of fibers in different stages of myelin development revealed that alcohol exposure caused a delay in myelin acquisition at 10 and 15 days that was compensated for at 20 and 90 days. Myelin thickness as a function of axon diameter was decreased in the alcohol exposed animals from 10 through 90 days, indicating a permanent reduction in the relative thickness of myelin. These results show that alcohol exposure for all of gestation and 10 postnatal days in the rat (human three trimester equivalency) causes a permanent reduction in myelin thickness along with a delay in myelin acquisition in the optic nerve. Such alterations in developing and adult myelin could help to explain some of the neurological and visual dysfunctions associated with developmental alcohol exposures.
本研究评估了孕期及产后10天酒精暴露(相当于人类孕期三个阶段)对大鼠视神经髓鞘和轴突发育的影响。大鼠在孕期通过液体饲料接触酒精,然后对其人工饲养的幼崽通过胃造口术喂食含乙醇的饲料,进一步暴露10天。来自配对喂养母鼠的对照动物在配对喂养的等热量饲料上人工饲养10天。在妊娠第(G)15天和20天以及出生后第(P)5天、10天、15天、20天和90天,对麻醉的动物进行固定剂灌注,然后制备视神经组织用于电子显微镜检查。在暴露于乙醇的动物中,从妊娠第20天到出生后第90天,视神经横截面积通常较小。每单位面积有髓神经纤维数量以及处于不同髓鞘发育阶段的纤维数量计数显示,酒精暴露在出生后10天和15天导致髓鞘形成延迟,但在20天和90天得到补偿。在暴露于酒精的动物中,从出生后10天到90天,髓鞘厚度与轴突直径的函数关系降低,表明髓鞘相对厚度永久性降低。这些结果表明,大鼠在整个孕期和产后10天暴露于酒精(相当于人类孕期三个阶段)会导致视神经髓鞘厚度永久性降低以及髓鞘形成延迟。发育中和成年期髓鞘的这种改变有助于解释一些与发育性酒精暴露相关的神经和视觉功能障碍。