We have been successful in identifying, in an acute-exposure mouse model, specific cell populations in early embryos (gestational days 7 - 9 1/2) that are selectively vulnerable to the cytotoxic effects of ethanol. The genesis of subsequent major malformations (including anencephaly, a number of facial malformations including cleft lip, limb reduction defects, and urinary tract abnormalities) can be explained based on the loss of the identified selectively vulnerable progenitor cell populations. We plan to extend our studies with particular attention to the developing brain. To evaluate the induced perturbations, we propose to: 1) comprehensively map vulnerable cell populations in the brains of later stage embryos; 2) compare, using fluorescence recovery after photobleaching (FRAP), membrane fluidity in vulnerable versus non-vulnerable neuronal cell populations within and between sensitive and resistant mouse strains in the presence or absence of ethanol; 3) attempt, using antioxidants, to ameliorate lipid peroxidation and cell death induced by ethanol in whole embryo culture and in vivo; and 4) determine the effect of excessive antioxidant (superoxide dismutase) activity in transgenic mice relative to ethanol-induced teratogenicity. The proposed studies will help us to understand (with special attention to mechanisms of action) the teratogenic effects of this drug of abuse. They will identify vulnerable neural populations, providing important information relative to expected outcomes in children born to women exposed to ethanol during the first trimester of pregnancy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
2R01AA008204-04
Application #
2044351
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1989-07-01
Project End
1996-06-30
Budget Start
1992-07-01
Budget End
1993-06-30
Support Year
4
Fiscal Year
1992
Total Cost
Indirect Cost
Name
University of North Carolina Chapel Hill
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
078861598
City
Chapel Hill
State
NC
Country
United States
Zip Code
27599
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