Although it has been 25 years since fetal alcohol syndrome (FAS) was first defined, it is still not clear whether or not the embryo suffers long-term brain deficits after alcohol exposure early in gestation. Since many women are binge drinkers, including those who can stop or significantly reduce their alcohol consumption once they are aware they are pregnant, and since many of them will not know they are pregnant for at least several weeks after conception, binge drinking during this early period may represent a very dangerous practice. Alarmingly, recent studies have provided evidence that contradicts the commonly held view that early pregnancy is not a vulnerable period for inducing birth defects. Therefore, until we understand the consequences of such exposure, misconceptions about the vulnerability of the conceptus during early development increases the likelihood of alcohol related birth defects, and delays the chances that the cause of those birth defects will be identified. This competitive renewal application represents the first comprehensive attempt to evaluate the effects of binge-like alcohol exposure during different discrete developmental events early in pregnancy on long-term structure and function of the brain. First, it utilizes the C57BL/6J mouse, which is known to be susceptible to alcohol-induced craniofacial and brain dysmorphology associated with FAS. Second, the timing of the alcohol exposure will focus on discrete embryonic events. Third by using a standard series of peak blood alcohol concentrations, it will be possible to compare the """"""""relative vulnerability"""""""" of different early prenatal periods. The studies will determine whether embryos exposed to alcohol during early development, even at blood alcohol concentrations (BACs) below that resulting in facial dysmorphology, nevertheless display lasting central nervous system dysfunction.
Specific Aim #1 will evaluate the effects of oral alcohol exposure occurring during gastrulation (gestation day [GD] 7:0) on fetal (GD14:0) somatic growth, brain morphology and craniofacial anomalies, to determine the threshold at which brain deficits may be induced in the absence of craniofacial dysmorphology.
Specific Aim #2 will evaluate the effects of alcohol exposure during specific developmental events from fertilization to early gestation.
Specific Aim #3 will test the hypothesis that binge-like alcohol exposure that is time-locked to specific developmental events early in development will have more deleterious effects than will similar duration of alcohol exposure that specifically misses the critical events identified in Specific Aim #2. The results will be beneficial for counseling women about the risks of drinking during the initial weeks of pregnancy, and may help to explain the variation in brain damage observed in children damaged by in utero alcohol exposure. The studies also will provide the foundation for mechanistic studies to identify how alcohol exposure damages the developing conceptus.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA010090-09
Application #
6604299
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Foudin, Laurie L
Project Start
1994-09-29
Project End
2006-06-30
Budget Start
2003-07-01
Budget End
2006-06-30
Support Year
9
Fiscal Year
2003
Total Cost
$270,000
Indirect Cost
Name
Texas A&M University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
141582986
City
College Station
State
TX
Country
United States
Zip Code
77845
Yang, Lingyu; Liu, Shuyun; Ding, Jinmei et al. (2017) Gut Microbiota Co-microevolution with Selection for Host Humoral Immunity. Front Microbiol 8:1243
Oladehin, Akinniran; Margret, Cecilia P; Maier, Susan E et al. (2007) Early postnatal alcohol exposure reduced the size of vibrissal barrel field in rat somatosensory cortex (SI) but did not disrupt barrel field organization. Alcohol 41:253-61
Parnell, Scott E; Ramadoss, Jayanth; Delp, Michael D et al. (2007) Chronic ethanol increases fetal cerebral blood flow specific to the ethanol-sensitive cerebellum under normoxaemic, hypercapnic and acidaemic conditions: ovine model. Exp Physiol 92:933-43
Livy, Daniel J; Maier, Susan E; West, James R (2004) Long-term alcohol exposure prior to conception results in lower fetal body weights. Birth Defects Res B Dev Reprod Toxicol 71:135-41
Livy, D J; Miller, E Kathryn; Maier, Susan E et al. (2003) Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the developing rat hippocampus. Neurotoxicol Teratol 25:447-58
Maier, Susan E; West, James R (2003) Alcohol and nutritional control treatments during neurogenesis in rat brain reduce total neuron number in locus coeruleus, but not in cerebellum or inferior olive. Alcohol 30:67-74
Livy, Daniel J; Parnell, Scott E; West, James R (2003) Blood ethanol concentration profiles: a comparison between rats and mice. Alcohol 29:165-71
Livy, D J; Maier And, S E; West, J R (2001) Fetal alcohol exposure and temporal vulnerability: effects of binge-like alcohol exposure on the ventrolateral nucleus of the thalamus. Alcohol Clin Exp Res 25:774-80
Maier, S E; West, J R (2001) Regional differences in cell loss associated with binge-like alcohol exposure during the first two trimesters equivalent in the rat. Alcohol 23:49-57
Maier, S E; Miller, J A; West, J R (1999) Prenatal binge-like alcohol exposure in the rat results in region-specific deficits in brain growth. Neurotoxicol Teratol 21:285-91

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