Cell population depletion associated with fetal alcohol brain damage: mechanisms of BAC-dependent cell loss.
Cell population depletion associated with fetal alcohol brain damage: mechanisms of BAC-dependent cell loss.
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与胎儿酒精脑损伤相关的细胞群耗竭：BAC 依赖性细胞损失的机制。
DOI：
10.1111/j.1530-0277.1990.tb01820.x
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发表时间：
1990
期刊：
影响因子：
--
通讯作者：
Marcussen,BL
中科院分区：
文献类型：
--
作者：
West,JR;Goodlett,CR;Bonthius,DJ;Hamre,KM;Marcussen,BL
神经元死亡是发育过程中酒精暴露最严重的后果之一。本文所描述的研究使用了一个新生大鼠模型来研究在大脑快速生长期酒精暴露导致神经元死亡的影响因素，并将这些因素与可能的损伤机制联系起来。血液酒精浓度(BAC)的分布是影响大脑生长缺陷和神经元死亡的一个重要变量-如果以类似暴饮暴食的方式摄入酒精，从而产生相对较高的BAC，则每天较小剂量的酒精可能比较大剂量的酒精更具破坏性。一天的酒精暴露也可能是有害的，如果获得高BAC，会导致大脑发育障碍和神经元丢失。在给定的大脑区域内，不同的大脑区域和不同的神经元群体表现出不同程度的脆弱性。一些神经元的丢失显然是由于酒精的直接作用导致的细胞死亡的功能，而其他的缺陷可能是由于酒精侮辱的初级或次级影响。在小脑中，成熟或代谢因子似乎也与酒精诱导的神经元死亡有关。使用抗微管相关蛋白2(MAP2)的单抗进行的免疫细胞化学研究表明，含有正在伸展树突的浦肯野细胞的小脑小叶比含有成熟较晚的浦肯野细胞的小叶更容易受到酒精的影响。大脑发育期间的酒精暴露可能会以多种方式产生神经元磨损，包括破坏细胞膜的完整性，抑制蛋白质合成或其他变化，如脂类溶解，或通过破坏细胞骨架元素。
Neuronal death is one of the most serious consequences of alcohol exposure during development. Studies described in this paper used a neonatal rat model to address factors affecting neuronal death following alcohol exposure during the period of rapid brain growth, and relate them to possible mechanisms of damage. The profile of blood alcohol concentrations (BACs) is an important variable influencing both brain growth deficits and neuronal death—a smaller daily dose of alcohol can be more damaging than a larger daily dose, if it is consumed in a binge‐like pattern that produces relatively higher BACs. Alcohol exposure for a single day also can be damaging, producing both brain growth deficits and neuron loss, if high BACs are obtained. Various brain regions and different neuronal populations within a given brain area exhibit different degrees of vulnerability. Some neuronal loss clearly is a function of cell death due to direct effects of alcohol, while other deficits may be due to either primary or secondary effects of the alcohol insult. In the cerebellum, a maturational or metabolic factor also appears to be involved with alcohol‐induced neuronal death. Immunocytochemical studies using a monoclonal antibody against microtubule‐associated protein 2 (MAP2) indicated that cerebellar lobules containing Purkinje cells that are in the process of extending dendrites are ones that are more vulnerable to alcohol than lobules containing Purkinje cells that mature later. Alcohol exposure during brain development may be producing neuron attrition in multiple ways, including disruption of membrane integrity, inhibition of protein synthesis or other alterations such as lipid solubility, or by disruption of cytoskeletal elements.