Effects of ethanol on cell cycle regulation and DNA repair in neural progenitors.

乙醇对神经祖细胞细胞周期调节和 DNA 修复的影响。

• 批准号: 7670939
• 负责人: Steven D Hicks
• 金额: $ 3.04万
• 依托单位: UPSTATE MEDICAL UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-05-25 至 2012-05-24
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7670939
• 关键词: Affect; Alcohol consumption; Alcoholism; Alcohols; Anaphase; Brain; Bromodeoxyuridine; Cell Count; Cell Cycle; Cell Cycle Kinetics; Cell Cycle Progression; Cell Cycle Regulation; Cell Proliferation; Cells; Cerebellum; Chromosomes; Chronic; Comet Assay; Complementary DNA; Corpus striatum structure; Cyclins; DNA; DNA Damage; DNA Repair; DNA Repair Enzymes; DNA Repair Pathway; DNA biosynthesis; Data; Development; Disease; Down-Regulation; Ethanol; Fetal Alcohol Spectrum Disorder; Gene Expression; Genes; Genetic Transcription; Genomics; Goals; Hippocampus (Brain); Immunoblotting; Impairment; In Situ Nick-End Labeling; In Vitro; Knowledge; Label; Lead; Learning; Maintenance; Measurable; Microcephaly; Microscopy; Mitotic spindle; Monitor; NS-5; Neuraxis; Neurologic; Neurons; Normal Cell; PTTG1 gene; Pathway interactions; Phase; Play; Proliferating; Protein Family; Protein p53; Research; Research Personnel; Reverse Transcriptase Polymerase Chain Reaction; Role; Signal Transduction; Staining method; Stains; Suspension substance; Suspensions; TP53 gene; Techniques; Time; Transcript; alcohol consumption during pregnancy; alcohol effect; alcohol exposure; alcohol response; cell motility; cellular development; embryonic stem cell; fetal; genetic regulatory protein; human PTTG1 protein; nerve stem cell; p53 Signaling Pathway; programs; protein expression; psychologic; repaired; research study; response; segregation; vector

DESCRIPTION (provided by applicant): The teratogenic effects of alcohol consumption on the developing brain can lead to devastating structural, neurologic, and psychologic impairments. The primary goal of this project is to learn how ethanol exerts its effects on brain development by exploring the relationship between ethanol exposure, DNA repair, and cell cycle regulation. Our hypothesis is that ethanol inhibits proliferation of neural stem cells through disruption of genomic replication and repair by cell cycle regulatory molecules. We will approach this issue by investigating the effects of variable ethanol exposure on the cell cycle kinetics, genomic damage, and differential gene transcription of neural stem cells (NSCs). We will also explore the role of the securin gene (PTTG1) in ethanol-induced changes in NSCs. We will study the effects of increased securin expression on NSC proliferation and DNA-repair pathways following ethanol exposure. This research will provide a greater understanding of the mechanisms by which alcohol impairs brain development and cellular division. Such knowledge has widespread applications in fetal alcohol spectrum disorder, or chronic alcoholism.

描述（由申请人提供）：酒精对发育中的大脑的致畸作用可导致破坏性的结构、神经和心理损伤。该项目的主要目标是通过探索乙醇暴露、DNA修复和细胞周期调节之间的关系，了解乙醇如何对大脑发育产生影响。我们的假设是乙醇通过破坏基因组复制和细胞周期调节分子的修复来抑制神经干细胞的增殖。我们将通过研究可变乙醇暴露对神经干细胞（NSCs）细胞周期动力学、基因组损伤和差异基因转录的影响来解决这个问题。我们还将探讨安全蛋白基因（PTTG1）在乙醇诱导的NSCs变化中的作用。我们将研究乙醇暴露后安全蛋白表达增加对NSC增殖和dna修复途径的影响。这项研究将使我们对酒精损害大脑发育和细胞分裂的机制有更深入的了解。这些知识在胎儿酒精谱系障碍或慢性酒精中毒中有广泛的应用。