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.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Individual Predoctoral NRSA for M.D./Ph.D. Fellowships (ADAMHA) (F30)
Project #
1F30AA018223-01
Application #
7670939
Study Section
Health Services Research Review Subcommittee (AA)
Program Officer
Matochik, John A
Project Start
2009-05-25
Project End
2012-05-24
Budget Start
2009-05-25
Budget End
2010-05-24
Support Year
1
Fiscal Year
2009
Total Cost
$30,388
Indirect Cost
Name
Upstate Medical University
Department
Other Basic Sciences
Type
Schools of Medicine
DUNS #
058889106
City
Syracuse
State
NY
Country
United States
Zip Code
13210
Hicks, Steven D; Miller, Michael W (2011) Effects of ethanol on transforming growth factor ?1-dependent and -independent mechanisms of neural stem cell apoptosis. Exp Neurol 229:372-80
Hicks, Steven D; Middleton, Frank A; Miller, Michael W (2010) Ethanol-induced methylation of cell cycle genes in neural stem cells. J Neurochem 114:1767-80