Astrocyte-derived factors modulate the inhibitory effect of ethanol on dendritic development.
Astrocyte-derived factors modulate the inhibitory effect of ethanol on dendritic development.
复制标题
星形胶质细胞衍生因子调节乙醇对树突发育的抑制作用。
作者：
Yanni,PenelopeA;Rising,LisaJ;Ingraham,ChristineA;Lindsley,TaraA
大量体内和体外研究表明乙醇会破坏神经形态发生。然而，尚未确定非神经元细胞在介导这种效应中起什么作用（如果有的话）。我们最近报道，乙醇抑制胎鼠海马锥体神经元低密度培养物中的树突发育（Yanni 和 Lindsley，2000：Dev Brain Res 120：233-243）。在该培养系统中，皮质星形胶质细胞在添加神经元之前将神经元培养基预处理2天，然后神经元在与星形胶质细胞共培养的单独基质上发育。为了确定星形胶质细胞对乙醇的反应是否介导乙醇对神经元的影响，本研究比较了在含有 400 mg/dl 乙醇的培养基中与活星形胶质细胞共培养以及在从未接触过乙醇的星形胶质细胞的条件培养基中 6 天后神经元的树突发育。在星形胶质细胞预处理培养基期间，在存在和不存在乙醇的情况下也进行了相同的实验。乙醇的作用因添加到培养物中的时间相对于添加新解离的神经元的时间而异。然而，乙醇的影响与神经元是否与活星形胶质细胞共培养无关。当星形胶质细胞正常预调节培养基时，铺板时添加的乙醇会抑制神经元的树突发育，无论它们是与活星形胶质细胞共培养还是在条件培养基中维持。令人惊讶的是，尽管培养基中继续存在乙醇，但在星形胶质细胞预处理培养基期间乙醇的存在对随后的树突发育具有生长促进作用。因此，星形胶质细胞响应乙醇释放可溶性因子，可以保护神经元免受乙醇对树突生长的抑制作用，但神经元暴露于这些因子的时间或其浓度可能会影响它们的活性。 GLIA 38:292–302, 2002。© 2002 Wiley-Liss, Inc.
Numerous studies in vivo and in vitro have demonstrated that ethanol disrupts neuromorphogenesis. However, it has not been determined what role, if any, is played by non‐neuronal cells in mediating this effect. We recently reported that ethanol inhibits dendritic development in low‐density cultures of fetal rat hippocampal pyramidal neurons (Yanni and Lindsley, 2000: Dev Brain Res 120:233–243). In this culture system, cortical astrocytes precondition neuronal culture media for 2 days before the addition of neurons, which then develop on a separate substrate in coculture with the astrocytes. To determine whether astrocyte response to ethanol mediates the effects of ethanol on neurons, the present study compared dendritic development of neurons after 6 days in medium containing 400 mg/dl ethanol in coculture with live astrocytes and in conditioned medium from astrocytes that were never exposed to ethanol. The same experiment was also performed with and without ethanol present during astrocyte preconditioning of the medium. The effects of ethanol differed depending on when it was added to the cultures relative to addition of newly dissociated neurons. However, the effects of ethanol were not related to whether neurons were cocultured with live astrocytes. When astrocytes preconditioned the medium normally, ethanol added at plating inhibited dendritic development of neurons regardless of whether they were maintained in coculture with live astrocytes or in conditioned medium. In surprising contrast, the presence of ethanol during astrocyte preconditioning of the media had a growth promoting effect on subsequent dendrite development despite the continued presence of ethanol in the medium. Thus, astrocytes release soluble factors in response to ethanol that can protect neurons from the inhibitory effects of ethanol on dendritic growth, but the timing of neuronal exposure to these factors, or their concentration, may influence their activity. GLIA 38:292–302, 2002. © 2002 Wiley‐Liss, Inc.