Yang Jun, Zoeller R Thomas
Biology Department and Molecular and Cellular Biology Program, Morrill Science Center, University of Massachusetts, Amherst, MA 01003, USA.
Brain Res Dev Brain Res. 2002 Oct 20;138(2):117-33. doi: 10.1016/s0165-3806(02)00461-3.
Fetal alcohol exposure is the most common nonhereditary cause of mental retardation in the western world. Rats prenatally treated with ethanol liquid diet exhibit extensive defects in the brain that accurately model those observed in humans. To analyze the ethanol effects on gene expression during brain development, we performed mRNA differential display and two-dimensional electrophoresis on gestational day (G) 13 and G 16 brain from rats treated with ethanol liquid diet. Using mRNA differential display followed by a variety of quantitative analyses, three genes were confirmed to be ethanol-responsive. Among them was Neuroendocrine-Specific Protein-A (NSP-A), which is known to be affected by thyroid hormone in the cortex at this developmental time. However, two additional genes known to be thyroid hormone-responsive were unaffected by ethanol, indicating that interference with thyroid hormone action may not be a predominant pathway by which alcohol induces damage in the fetal brain. The observation that interferon-inducible protein-10 (IP-10) is up-regulated in ethanol-treated fetal brain may indicate the presence of a disease process recruiting CD8+ T-cells capable of interfering with myelination. The result of two-dimensional (2D) electrophoresis and Western analyses demonstrated that few changes in the abundance of individual proteins or the phosphorylation of proteins at threonine and tyrosine were induced by prenatal ethanol exposure. A critical analysis of the approaches used in the present study may be important for future studies in this field.
在西方世界，胎儿酒精暴露是智力迟钝最常见的非遗传性病因。用乙醇液体饲料进行产前处理的大鼠，其大脑呈现出广泛的缺陷，这些缺陷精确模拟了在人类身上观察到的情况。为了分析乙醇对大脑发育过程中基因表达的影响，我们对用乙醇液体饲料处理的大鼠在妊娠第13天（G13）和第16天（G16）的大脑进行了mRNA差异显示和二维电泳分析。通过mRNA差异显示并结合各种定量分析，证实有三个基因对乙醇有反应。其中包括神经内分泌特异性蛋白-A（NSP-A），已知在这个发育阶段，该蛋白在皮质中会受到甲状腺激素的影响。然而，另外两个已知对甲状腺激素有反应的基因不受乙醇影响，这表明干扰甲状腺激素作用可能不是酒精诱导胎儿脑损伤的主要途径。在乙醇处理的胎儿脑中，干扰素诱导蛋白-10（IP-10）上调这一观察结果可能表明存在一种招募能够干扰髓鞘形成的CD8 + T细胞的疾病过程。二维（2D）电泳和蛋白质免疫印迹分析结果表明，产前乙醇暴露几乎没有引起单个蛋白质丰度或苏氨酸和酪氨酸位点蛋白质磷酸化的变化。对本研究中所用方法进行批判性分析可能对该领域未来的研究很重要。
