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低剂量乙醇会影响小脑混合长期胚胎培养中所有类型的细胞。

A low ethanol dose affects all types of cells in mixed long-term embryonic cultures of the cerebellum.

机构信息

Functional Pharmacology, Department of Neuroscience, Uppsala University, Uppsala, Sweden.

出版信息

Basic Clin Pharmacol Toxicol. 2010 Jun;106(6):472-8. doi: 10.1111/j.1742-7843.2009.00528.x. Epub 2010 Jan 14.

Abstract

The beneficial effect of the '1-drink-a-day' lifestyle is suggested by studies of cardiovascular health, and this recommendation is increasingly followed in many countries. The main objective of this study was to determine whether this pattern of ethanol use would be detrimental to a pregnant woman. We exposed a primary culture of rat cerebellum from embryonic day 17 (corresponding to second trimester in humans) to ethanol at a concentration of 17.6 mM which is roughly equivalent to one glass of wine. Acutely, there was no change in cell viability after 5 or 8 days of exposure relative to control. By 11 days, a reduction in the number of viable cells was observed without an accompanying change in caspase-3 activity (marker of apoptotic cell death), suggesting changes in cell proliferation. As the proportion of nestin-positive cells was higher in the ethanol-treated cultures after 5 days, we hypothesized that an increase in differentiation to neurons would compensate for the ongoing neuronal death. However, there were limits to this compensatory ability as the relative proportion of nestin-positive cells was decreased after 11 days. To further illustrate the negative long-term effects of this ethanol dose, cultures were exposed for 30 days. After this period, virtually no neurons or myelinating oligodendrocytes were present in the ethanol-treated cultures. In conclusion, chronic exposure to ethanol, even at small doses, dramatically and persistently affects normal development.

摘要

“每天一杯”的生活方式对心血管健康有益,这一建议在许多国家越来越受到推崇。本研究的主要目的是确定这种乙醇使用模式是否对孕妇有害。我们将来自胚胎第 17 天(相当于人类妊娠中期)的大鼠小脑原代培养物暴露于 17.6mM 的乙醇浓度下,这大致相当于一杯葡萄酒。与对照组相比,暴露于乙醇 5 或 8 天后,细胞活力没有变化。到第 11 天,观察到存活细胞数量减少,但 caspase-3 活性(细胞凋亡的标志物)没有变化,提示细胞增殖发生变化。由于在乙醇处理的培养物中,巢蛋白阳性细胞的比例在第 5 天更高,我们假设向神经元分化的增加将补偿持续的神经元死亡。然而,这种代偿能力是有限的,因为在第 11 天后,巢蛋白阳性细胞的相对比例降低。为了进一步说明这种乙醇剂量的长期负面影响,我们将培养物暴露 30 天。经过这段时间,在乙醇处理的培养物中几乎没有神经元或少突胶质细胞存在。总之,慢性暴露于乙醇,即使是小剂量,也会对正常发育产生显著和持久的影响。

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