Effects of prenatal exposure to ethanol on the expression of bcl-2, bax and caspase 3 in the developing rat cerebral cortex and thalamus
Effects of prenatal exposure to ethanol on the expression of bcl-2, bax and caspase 3 in the developing rat cerebral cortex and thalamus
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DOI：
10.1016/s0006-8993(01)02718-4
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发表时间：
2001-08-17
期刊：
影响因子：
2.9
通讯作者：
Miller, MW
中科院分区：
文献类型：
--
作者：
Mooney, SM;Miller, MW
产前暴露于乙醇导致体感皮层神经元死亡，但显然不是在丘脑腹侧基底核。效应子如bcl-2、bax和caspase 3可以决定神经元的存活或死亡。我们假设，乙醇差异影响这些蛋白质在皮质和丘脑的表达，在自然发生的和乙醇诱导的神经元死亡期间。妊娠大鼠自由采食含乙醇的流质饮食（Et）或成对饲喂等热量的非酒精性饮食（Ct）。从胎仔（妊娠第16天和第19天）和幼仔（出生后第0天（P）至P30）采集样本，并使用定量免疫印迹法检测bcl-2、bax或caspase 3表达。产前暴露于乙醇减少皮质bcl-2的表达，但不Bax表达P6。因此，bcl-2/bax比值在ET处理的大鼠中低于对照组。相反，两组大鼠丘脑bcl-2和bax的表达均无显著差异。因此，丘脑bcl-2/bax的比例不受乙醇暴露的影响。在自然发生的神经元死亡期间，在ET处理的大鼠的皮质中，caspase 3的活性（20 kDa）和非活性亚型（32 kDa）的表达发生了改变，但在丘脑中没有。因此，产前暴露于乙醇影响出生后早期的死亡相关蛋白质在大脑皮层的表达，但不是在丘脑。这些生化变化与发育中CNS中乙醇毒性的空间和时间选择性的解剖学数据一致。(C)2001 Elsevier Science B. V.保留所有权利。
Prenatal exposure to ethanol causes neuronal death in somatosensory cortex, but apparently not in the ventrobasal nucleus of the thalamus. Effectors such as bcl-2, bax, and caspase 3 can determine whether a neuron survives or dies. We hypothesize that ethanol differentially affects the expression of these proteins in the cortex and thalamus during the periods of naturally occurring and ethanol-induced neuronal death. Pregnant rats were fed ad libitum with an ethanol-containing liquid diet (Et) or pair-fed an isocaloric non-alcoholic diet (Ct). Samples were collected from fetuses (gestational day (G) 16 and G19) and pups (postnatal day (P) 0 through P30) and examined for bcl-2, bax, or caspase 3 expression using a quantitative immunoblotting procedure. Prenatal exposure to ethanol reduced cortical bcl-2 expression, but not bax expression on P6. Hence, the bcl-2/bax ratio was lower in Et-treated rats than in controls. In contrast, thalamic expression of neither bcl-2 nor bax was significantly different in the two groups of rats. Thus, the thalamic bcl-2/bax ratio was unaffected by exposure to ethanol. During the period of naturally occurring neuronal death, the expression of the active (20 kDa) and inactive isoforms (32 kDa) of caspase 3 was altered in the cortices of Et-treated rats, but not in their thalami. Thus, prenatal exposure to ethanol affected the early postnatal expression of death-related proteins in the cortex, but not in the thalamus. These biochemical changes concur with anatomical data on the spatial and temporal selectivity of ethanol toxicity in the developing CNS. (C) 2001 Elsevier Science B.V. All rights reserved.