Dheen S T, Hao A J, Fu J, Gopalakrishnakone P, Ling E A
Molecular Neurobiology Laboratory, Department of Anatomy, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Histol Histopathol. 2007 Jul;22(7):729-42. doi: 10.14670/HH-22.729.
In an attempt to understand the molecular basis underlying the neural tube defects induced by the teratogen, cyclophosphamide (CP), cDNA microarray analysis was carried out in neural tubes of embryos derived from normal and CP-treated rats. Genes found to have altered expression levels in CP-treated group were clustered into groups on the basis of their biological functions. The expression profile of different genes involved in transcription of molecules related to cell adhesion, inflammation, metabolism and neurotrophic factors pathways as well as in still undefined processes was differentially affected by the teratogen treatment. The most remarkable change was the up-regulation of genes related to an inflammatory process dominated by the fetal brain macrophages viz. amoeboid microglia. Amoeboid microglia/brain macrophage expansion, based on gene expression and histological analysis, was found to be vigorous at the subventricular region. The present results suggest that a vigorous inflammatory response involving amoeboid microglia/brain macrophages primarily is an important component in CP-induced prenatal development disorder.
为了了解致畸剂环磷酰胺（CP）诱发神经管缺陷的分子基础，对正常大鼠和经CP处理的大鼠胚胎的神经管进行了cDNA微阵列分析。在CP处理组中发现表达水平发生改变的基因，根据其生物学功能被聚类分组。致畸剂处理对涉及细胞黏附、炎症、代谢和神经营养因子途径以及仍未明确的过程的分子转录的不同基因的表达谱产生了不同影响。最显著的变化是与以胎儿脑巨噬细胞即阿米巴样小胶质细胞为主导的炎症过程相关的基因上调。基于基因表达和组织学分析，发现阿米巴样小胶质细胞/脑巨噬细胞在脑室下区域的扩增很活跃。目前的结果表明，主要涉及阿米巴样小胶质细胞/脑巨噬细胞的强烈炎症反应是CP诱导的产前发育障碍的一个重要组成部分。
