Division of Medical Sciences, University of Victoria, Victoria, BC, Canada; Department of Drug Design and Pharmacology, Faculty of Health and Medical Sciences, University of Copenhagen, Denmark.
Hippocampus. 2014 Jan;24(1):54-64. doi: 10.1002/hipo.22203. Epub 2013 Oct 4.
Alcohol consumption during pregnancy is deleterious to the developing brain of the fetus and leads to persistent deficits in adulthood. Long-term potentiation (LTP) is a biological model for learning and memory processes and previous evidence has shown that prenatal ethanol exposure (PNEE) affects LTP in a sex specific manner during adolescence. The objective of this study was to determine if there are sex specific differences in adult animals and to elucidate the underlying molecular mechanisms that contribute to these differences. Pregnant Sprague-Dawley dams were assigned to either; liquid ethanol, pair-fed or standard chow diet. In vivo electrophysiology was performed in the hippocampal dentate gyrus (DG) of adult offspring. LTP was induced by administering 400 Hz stimuli. Western blot analysis for glutamine synthetase (GS) and glutamate decarboxylase from tissue of the DG indicated that GS expression was increased following PNEE. Surprisingly, adult females did not show any deficit in N-methyl-D-aspartate (NMDA)-dependent LTP after PNEE. In contrast, males showed a 40% reduction in LTP. It was indicated that glutamine synthetase expression was increased in PNEE females, suggesting that altered excitatory neurotransmitter replenishment may serve as a compensatory mechanism. Ovariectomizing females did not influence LTP in control or PNEE animals, suggesting that circulating estradiol levels do not play a major role in maintaining LTP levels in PNEE females. These results demonstrate the sexually dimorphic effects of PNEE on the ability for the adult brain to elicit LTP in the DG. The mechanisms for these effects are not fully understood, but an increase in glutamine synthetase in females may underlie this phenomenon.
怀孕期间饮酒对胎儿发育中的大脑有害，并导致成年后持续出现缺陷。长时程增强（LTP）是学习和记忆过程的生物学模型，先前的证据表明，产前乙醇暴露（PNEE）以性别特异性的方式在青春期影响 LTP。本研究的目的是确定成年动物是否存在性别特异性差异，并阐明导致这些差异的潜在分子机制。将怀孕的 Sprague-Dawley 母鼠分配到以下组别：液体乙醇、配对喂养或标准饲料。在成年后代的海马齿状回（DG）中进行体内电生理学。通过给予 400 Hz 刺激来诱导 LTP。DG 组织的谷氨酰胺合成酶（GS）和谷氨酸脱羧酶的 Western blot 分析表明，PNEE 后 GS 表达增加。令人惊讶的是，PNEE 后成年雌性的 N-甲基-D-天冬氨酸（NMDA）依赖性 LTP 没有任何缺陷。相比之下，雄性的 LTP 减少了 40%。表明 PNEE 雌性的谷氨酰胺合成酶表达增加，表明改变的兴奋性神经递质补充可能作为一种补偿机制。对雌性进行卵巢切除术不会影响对照或 PNEE 动物的 LTP，表明循环雌二醇水平在维持 PNEE 雌性的 LTP 水平方面不起主要作用。这些结果表明，PNEE 对成年大脑在 DG 中引发 LTP 的能力具有性别二态性影响。这些影响的机制尚未完全理解，但雌性中谷氨酰胺合成酶的增加可能是这种现象的基础。
