Barr Alasdair M, Hofmann Candace E, Phillips Anthony G, Weinberg Joanne, Honer William G
Center for Complex Disorders, Department of Psychiatry, University of British Columbia, Vancouver General Hospital Research Pavilion, Vancouver, Canada.
Alcohol Clin Exp Res. 2005 Nov;29(11):1915-20. doi: 10.1097/01.alc.0000187806.68957.0a.
Rodents that are prenatally exposed to ethanol have been shown to exhibit a wide range of cognitive deficits, including impairments in memory, attention and executive function. To determine a potential molecular substrate for cognitive dysfunction in adulthood, we measured regional levels of the presynaptic proteins complexin I and II in a rat model of prenatal ethanol exposure, as levels of these proteins are altered in cognitive-related synaptic plasticity.
Pregnant female rats received either a liquid ethanol diet (36% ethanol-derived calories) or a liquid control diet (maltose-dextrin isocalorically substituted for ethanol, matched in amount [g/kg body wt/day of gestation] to an ethanol-consuming partner), or were given ad libitum-fed access to standard laboratory chow and water. Levels of complexin I, II and the ubiquitous presynaptic marker synaptophysin were measured in the frontal cortex and hippocampus of adult male offspring, using ELISA.
Prenatal exposure to ethanol did not alter levels of presynaptic proteins in the hippocampus or levels of synaptophysin in the prefrontal cortex. However, rats prenatally exposed to ethanol displayed significantly lower levels of both complexin I and II in the prefrontal cortex compared to control animals.
These data indicate that prenatal exposure to ethanol is associated with a selective loss of complexin proteins in the frontal cortex. These proteins are known to be important for activity-dependent neurotransmission, and have previously been shown to mediate synaptic plasticity and cognition. These combined findings suggest that further study of complexin proteins as a substrate for cognitive impairment related to prenatal exposure to ethanol is warranted.
已证实，产前接触乙醇的啮齿动物会出现广泛的认知缺陷，包括记忆、注意力和执行功能受损。为了确定成年期认知功能障碍的潜在分子基础，我们在产前乙醇暴露大鼠模型中测量了突触前蛋白复合蛋白I和II的区域水平，因为这些蛋白的水平在与认知相关的突触可塑性中会发生改变。
怀孕的雌性大鼠接受液体乙醇饮食（36%乙醇热量）或液体对照饮食（麦芽糖糊精等热量替代乙醇，摄入量[克/千克体重/妊娠日]与摄入乙醇的配对动物匹配），或随意给予标准实验室饲料和水。使用酶联免疫吸附测定法（ELISA）测量成年雄性后代额叶皮质和海马体中复合蛋白I、II以及普遍存在的突触前标志物突触素的水平。
产前接触乙醇并未改变海马体中突触前蛋白的水平或前额叶皮质中突触素的水平。然而，与对照动物相比，产前接触乙醇的大鼠前额叶皮质中复合蛋白I和II的水平均显著降低。
这些数据表明，产前接触乙醇与额叶皮质中复合蛋白的选择性缺失有关。已知这些蛋白对依赖活动的神经传递很重要，并且先前已证明它们可介导突触可塑性和认知。这些综合发现表明，有必要进一步研究复合蛋白作为与产前接触乙醇相关的认知障碍的基础。
