Division of Life Science, College of Natural Sciences and Applied Life Science (Brain Korea 21), Gyeongsang National University, Chinju 660-701, South Korea.
Synapse. 2010 Jun;64(6):467-77. doi: 10.1002/syn.20752.
Prenatal ethanol exposure has various deleterious effects on neuronal development and can induce various defects in developing brain, resulting in fetal alcohol syndrome (FAS). gamma-Aminobutyric acid (GABA(B)) receptor (R) is known to play an important role during the development of the central nervous system (CNS). Our study was designed to investigate the effect of ethanol (100 mM), nicotine (50 microM) (for 30 min and 1 h), vitamin C (vitC, 0.5 mM), ethanol plus vitC, and nicotine plus vitC on expression level of GABA(B1), GABA(B2)R, and protein kinase A-alpha (PKA) in prenatal rat cortical and hippocampal neurons at gestational days (GD) 17.5. The results showed that, upon ethanol and nicotine exposure, GABA(B1) and GABA(B2)R protein expression increased significantly in the cortex and hippocampus for a short (30 min) and long term (1 h), whereas only GABA(B2)R subunit was decreased upon nicotine exposure for a long term in the cortex. Furthermore, PKA expression in cortex and hippocampus increased with ethanol exposure during short term, whereas long-term exposure results increased in cortex and decreased in hippocampus. Moreover, the cotreatment of vitC with ethanol and nicotine showed significantly decreased expression of GABA(B1), GABA(B2)R, and PKA in cortex and hippocampus for a long-term exposure. Mitochondrial membrane potential, Fluoro-jade-B, and propidium iodide staining were used to elucidate possible neurodegeneration. Our results suggest the involvement of GABA(B)R and PKA in nicotine and ethanol-mediated neurodevelopmental defects and the potential use of vitC as a effective protective agent for FAS-related deficits.
产前乙醇暴露对神经元发育有多种有害影响，并可导致发育中大脑出现各种缺陷，从而导致胎儿酒精综合征（FAS）。γ-氨基丁酸（GABA）B 型受体（R）在中枢神经系统（CNS）发育过程中起着重要作用。我们的研究旨在研究乙醇（100mM）、尼古丁（50μM）（30 分钟和 1 小时）、维生素 C（vitC，0.5mM）、乙醇加 vitC 和尼古丁加 vitC 对妊娠第 17.5 天孕鼠皮质和海马神经元中 GABA（B1）、GABA（B2）R 和蛋白激酶 A-α（PKA）表达水平的影响。结果表明，在乙醇和尼古丁暴露下，皮质和海马中的 GABA（B1）和 GABA（B2）R 蛋白表达在短期（30 分钟）和长期（1 小时）均显著增加，而尼古丁暴露仅在长期内皮质中的 GABA（B2）R 亚基减少。此外，在短期暴露时，PKA 在皮质和海马中的表达随乙醇暴露而增加，而长期暴露时，皮质中的表达增加，海马中的表达减少。此外，vitC 与乙醇和尼古丁的联合处理在长期暴露时，皮质和海马中 GABA（B1）、GABA（B2）R 和 PKA 的表达明显降低。线粒体膜电位、Fluoro-jade-B 和碘化丙啶染色用于阐明可能的神经退行性变。我们的结果表明，GABA（B）R 和 PKA 参与了尼古丁和乙醇介导的神经发育缺陷，vitC 可能作为治疗与 FAS 相关缺陷的有效保护剂。
