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Mechanisms of Fetal Alcohol Spectrum Disorders

Alcohol consumption during pregnancy can result in fetal alcohol spectrum
disorders (FASD), which encompass a range of physical, behavioral, learning, emotional
and social disturbances. Many mechanisms for this array of alcohol-derived fetal
injuries have been proposed, but none fully accounts for the deficiencies observed.
Alcohol is a ubiquitous drug that may affect the brain at any or all stages of development
and at multiple sites; regional differences in vulnerability of different brain structures
during different periods of exposure have been demonstrated.
This study investigates possible mechanisms for the alcohol induced
neurodevelopment damage seen as a result of prenatal alcohol exposure, and also
includes evaluation of a potential intervention strategy (glutamine). These experiments
all utilized the sheep model, which has distinct advantages over the rodent model for
third trimester-equivalent studies (a time of increased vulnerability to the effects of
alcohol).
The fetal hippocampal formation (pyramidal cells in the CA1 and CA2/3 fields
and granule cells of the dentate gyrus) and olfactory bulb (mitral cells) have been altered
in response to alcohol exposure in rodent model studies. This study examined the effects on the fetal hippocampal formation and olfactory bulb in response to all three
trimester-equivalent alcohol exposure in the sheep model, a species in which the third
trimester-equivalent occurs in utero (as opposed to post-natal as occurs in the rodent). It
is known that both maternal and fetal cortisol levels increase in response to alcohol. The
role of cortisol in mediating fetal cerebellar Purkinje cell loss (known to occur with
alcohol exposure) was analyzed. Lastly, the availability of circulating amino acids, both
maternal and fetal, in response to alcohol are reported. The results of administration of a
single acute dose of glutamine to the ewe, concurrent with alcohol, was evaluated for its
ability to prevent the amino acid and pH perturbations known to occur in response to
alcohol.

Identiferoai:union.ndltd.org:tamu.edu/oai:repository.tamu.edu:1969.1/ETD-TAMU-2010-08-8359
Date2010 August 1900
CreatorsWilson, Shannon Elizabeth
ContributorsCudd, Timothy
Source SetsTexas A and M University
Languageen_US
Detected LanguageEnglish
Typethesis, text
Formatapplication/pdf

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