Methanol exposure interferes with morphological cell movements in the Drosophila embryo and causes increased apoptosis in the CNS
Methanol exposure interferes with morphological cell movements in the Drosophila embryo and causes increased apoptosis in the CNS
复制标题
DOI：
10.1002/neu.20020
复制
发表时间：
2004-09-05
期刊：
影响因子：
--
通讯作者：
Liu, H
中科院分区：
文献类型：
--
作者：
Mellerick, DM;Liu, H
尽管组织培养和细菌模型对毒理学有重大贡献，但发育神经毒素的整体动物模型在可用性和实验容易性方面受到限制。由于果蝇是一种非常容易获得的胚胎发育模型，因此我们询问它是否可以用于研究甲醇发育神经毒性。在存在4%甲醇的情况下，约35%的胚胎死亡，并且甲醇暴露导致约一半胚胎中的严重CNS缺陷，其中纵向连接体背侧移位并且连合形成严重减少。此外，在其他胚层的形态缺陷的范围内被视为，和细胞运动受到不利影响的甲醇暴露。虽然我们没有发现任何证据表明，甲醇暴露影响神经母细胞的能力，分裂或诱导不适当的细胞凋亡，在中枢神经系统的胚带回缩胚胎，凋亡细胞核的数量显着增加，在甲醇暴露的胚胎相比，控制，特别是在和邻近腹侧中线。细胞凋亡对甲醇神经毒性有重要作用，因为缺乏细胞死亡基因grim、hid和reaper的胚胎比野生型胚胎具有由甲醇暴露引起的较轻的CNS缺陷。我们的数据表明，当神经元和神经胶质细胞受到甲醇暴露的严重不利影响时，受损的细胞通过凋亡被清除，导致胚胎死亡。因此，果蝇胚胎可能被证明是有用的，在识别和解开发育神经毒性，特别是与甲醇毒性的机制方面。(C)2004 Wiley Periodicals，Inc.
Despite the significant contributions of tissue culture and bacterial models to toxicology, whole animal models for developmental neurotoxins are limited in availability and ease of experimentation. Because Drosophila is a well understood model for embryonic development that is highly accessible, we asked whether it could be used to study methanol developmental neurotoxicity. In the presence of 4% methanol, approximately 35% of embryos die and methanol exposure leads to severe CNS defects in about half those embryos, where the longitudinal connectives are dorsally displaced and commissure formation is severely reduced. In addition, a range of morphological defects in other germ layers is seen, and cell movement is adversely affected by methanol exposure. Although we did not find any evidence to suggest that methanol exposure affects the capacity of neuroblasts to divide or induces inappropriate apoptosis in these cells, in the CNS of germ band retracted embryos, the number of apoptotic nuclei is significantly increased in methanol-exposed embryos in comparison to controls, particularly in and adjacent to the ventral midline. Apoptosis contributes significantly to methanol neurotoxicity because embryos lacking the cell death genes grim, hid, and reaper have milder CNS defects resulting from methanol exposure than wild-type embryos. Our data suggest that when neurons and glia are severely adversely affected by methanol exposure, the damaged cells are cleared by apoptosis, leading to embryonic death. Thus, the Drosophila embryo may prove useful in identifying and unraveling mechanistic aspects of developmental neurotoxicity, specifically in relation to methanol toxicity. (C) 2004 Wiley Periodicals, Inc.