Savage D D, Cruz L L, Duran L M, Paxton L L
Department of Neurosciences, School of Medicine, University of New Mexico Health Sciences Center, Albuquerque 87131-5223, USA.
Alcohol Clin Exp Res. 1998 Nov;22(8):1771-7.
Prenatal ethanol exposure has been associated with long-lasting intellectual impairments in children. Previous studies suggest that these deficits are, in part, linked to neurochemical abnormalities that reduce the ability to sustain long-term potentiation (LTP) in hippocampal formation of adult offspring. One presynaptic component of LTP that manifests during the first half-hour after tetanic stimulation is an enhancement of amino acid neurotransmitter release. Given that the onset of enhanced neurotransmitter release correlates temporally with the decay of hippocampal LTP in prenatal ethanol-exposed offspring, we tested the hypothesis that prenatal ethanol exposure reduces tetanus stimulus-induced potentiation of electrically evoked amino acid release in hippocampal slices. Rat dams consumed 1 of 3 diets throughout gestation: (1) a BioServ liquid diet containing 5% (v/v) ethanol (26% ethanol-derived calories) that produces a maternal peak blood ethanol concentration of 83 mg/dl; (2) pair-fed an isocalorically equivalent amount of 0% ethanol liquid diet; or (3) Purina rat chow ad libitum. Hippocampal slices were prepared from adult offspring from each experimental diet group. Neither the amount of hippocampal slice tissue protein nor the incorporation of [3H]-D-aspartate (D-ASP) was affected by prenatal ethanol exposure. Furthermore, spontaneous efflux and electrically evoked D-ASP release were similar among the three diet groups. However, tetanus stimulus-induced potentiation of evoked D-ASP release in prenatal ethanol-exposed offspring was reduced to about one-third of the potentiation of D-ASP release observed in the control diet groups. These results suggest that prenatal ethanol exposure produces long-lasting deficits in the neurochemical mechanisms responsible for activity-dependent potentiation of amino acid transmitter release without affecting the synaptic machinery responsible for amino acid uptake, storage, and release.
产前乙醇暴露与儿童长期智力损伤有关。先前的研究表明，这些缺陷部分与神经化学异常有关，这些异常会降低成年后代海马结构中维持长时程增强（LTP）的能力。LTP的一个突触前成分在强直刺激后的前半小时表现出来，即氨基酸神经递质释放增强。鉴于神经递质释放增强的起始时间与产前乙醇暴露后代海马LTP的衰减在时间上相关，我们测试了以下假设：产前乙醇暴露会降低破伤风刺激诱导的海马切片中电诱发氨基酸释放的增强。大鼠母鼠在整个妊娠期食用三种饮食中的一种：（1）含有5%（v/v）乙醇（26%乙醇衍生热量）的BioServ液体饮食，其母体血液乙醇峰值浓度为83mg/dl；（2）配对喂食等热量的0%乙醇液体饮食；或（3）随意食用普瑞纳大鼠饲料。从每个实验饮食组的成年后代制备海马切片。产前乙醇暴露对海马切片组织蛋白的量或[3H]-D-天冬氨酸（D-ASP）的掺入均无影响。此外，三种饮食组之间的自发流出和电诱发的D-ASP释放相似。然而，产前乙醇暴露后代中破伤风刺激诱导的诱发D-ASP释放增强降低至对照饮食组中观察到的D-ASP释放增强的约三分之一。这些结果表明，产前乙醇暴露在负责氨基酸递质释放的活动依赖性增强的神经化学机制中产生长期缺陷，而不影响负责氨基酸摄取、储存和释放的突触机制。
