EFFECT OF PRENATAL ALCOHOL EXPOSURE OF GGTP

多项研究表明，酗酒者和问题 饮酒者的血清伽马-谷氨酰胺水平高于正常水平 转肽酶(γ-GTP)。慢性饮酒者的动物模型已经被 显示出在几种疾病中伽马-谷氨酰转肽酶水平升高 大脑区域。母亲所生的老鼠摄入了35%的卡路里 在怀孕和哺乳期间，酒精的摄入量是 发现大脑中有较高水平的伽马-谷氨酰转肽酶 而不是他们的对照组的肝脏。此外，酒精的后代 接受治疗的母亲表现出许多畸形特征，如 胎儿酒精综合症。尽管伽马-GTP在大脑中的作用还没有 有证据表明，这种酶可能参与了 确定一个人对酒精和某些形式的酒精的敏感性 精神发育迟滞。结合在膜上的酶是 伽马-谷氨酰循环，它解释了谷胱甘肽的周转 (GSH)。伽玛-谷氨酰循环参与合成和 GSH的降解，涉及GSH的细胞外运输和 伽马-谷氨酰氨基酸进入细胞。伽玛-GTP活性的增加， 如酒精治疗后所见，可能是一种机制，通过它 抑制性神经递质GABA的浓度可能会增加。 它还可能导致谷胱甘肽周转增加。伽马-GTP的增加 活动可能是动物试图增加 合成谷胱甘肽以保护自己免受药物的毒性影响， 自由基和活性氧中间体。目前的研究是 为确定母体给药的效果而采取的措施 酒精对新生大鼠脑、肝及血清γ-GTP的影响。谷胱甘肽 还将测量大脑中的GABA水平。我们将研究 母体饮酒对小鼠胚胎个体发育的影响 并将决定GAMA-GTP的生化性质 已经被更改了。我们将测量幼崽大脑中的Gamma-GTP活性 从胎龄16天，到120天龄。雌性Wistar大鼠将 被饲养到成年雄性，并被放置在含有酒精或 等量的糊精形式的碳水化合物， 从怀孕第一天开始。尽管已经有很多研究 参与确定宫内给药的效果 酒精，大多数人直到怀孕后才给怀孕的母亲酒精 妊娠的前8天。我们打算在此期间进行酒精注射。 发展的关键时期。

Several studies have demonstrated that alcoholics, as well as problem drinkers, have higher than normal serum levels of Gamma-glutamyl transpeptidase (Gamma-GTP). Animal models of chronic drinkers have been shown to have elevated levels of Gamma-glutamyl transpeptidase in several brain areas. Rats born to mothers which received 35% of their caloric intake in the form of alcohol, both during gestation and lactation were found to have higher levels of Gamma-glutamyl transpeptidase in brain and liver than their controls. Additionally, the offspring of the alcohol treated mothers exhibited many of the dysmorphic characteristics seen in Fetal Alcohol Syndrome. Although the role of Gamma-GTP in brain has not been clarified, evidence suggests that the enzyme may involved in determining an individual's sensitivity to alcohol and in some forms of mental retardation. The membrane-bound enzyme is a vital part of the Gamma-glutamyl cycle, which accounts for the turnover of glutathione (GSH). The Gamma-glutamyl cycle is involved in the synthesis and degradation of GSH and involves transport of GSH out of cells and Gamma-glutamyl amino acids into cells. An increase in Gamma-GTP activity, such as is seen following alcohol treatment, may be a mechanism by which concentrations of GABA, an inhibitory neurotransmitter, may be increased. It may also produce an increased turnover of GSH. An increase in Gamma-GTP activity may be a reflection of the animal's attempt to increase glutathione synthesis to protect itself against the toxic effects of drugs, free radicals and reactive oxygen intermediates. The present study is undertaken to determine the effects of the maternal administration of alcohol on brain, liver and serum Gamma-GTP in neonatal rats. Glutathione and GABA levels in brain will also be measured. We will examine the effects of the maternal administration of alcohol on the ontogenesis of the enzyme and will determine whether the biochemical properties of Gamma-GTP have been altered. We will measure Gamma-GTP activity in brains of pups from gestational age 16 days, to 120 days of age. Female Wistar rats will be bred to adult males and placed on a liquid diet containing alcohol or an isocaloris equivalent amount of carbohydrate in the form of dextrin, starting on day one of gestation. Although there have been many studies involved with determining the effects of the in utero administration of alcohol, most have not given alcohol to the pregnant mothers until after the first 8 days of gestation. We intend to administer alcohol during this critical period of development.