Exposure of a fetus to ethanol can lead to the development of fetal alcohol syndrome, which is characterized by various morphological and behavioral deficits in fetal alcohol-exposed (FAE) offspring. These offspring often show clinical sleep-wake disturbances and abnormalities in the functions of the neuroendocrine system. Recent studies have identified the possibility that the sleep-wake disturbances and neuroendocrine function abnormalities in the FAE offspring are related to long-term changes in circadian clock mechanisms. Employing the rat animal model, this proposal determines whether fetal exposure to ethanol causes long- lasting changes in the circadian output of beta-endorphin neurons located in the arcuate nucleus of the hypothalamus and their regulation of plasma gonadotropin release. It tests the hypothesis that fetal exposure to ethanol causes an abnormality in the adult expression of the central clock mechanisms in the suprachaismatic nucleus of the hypothalamus leading to alteration in the internal clock mechanisms and the phasic hormonal output of beta-endorphin neurons. It also identifies whether fetal exposure to ethanol alters the molecular mechanism governing the photic responses of the central and internal clocks. The proposed research uses laser-captured microscopy, immunohistochemistry, Western blot, radioimmunoassay, and real-time RT-PCR techniques to identify gene and protein expressions that are critically involved in the regulation of central and internal clock mechanisms and the phasic hormonal outputs from beta-endorphin neurons. The proposed studies should provide a better understanding of the long-term consequences of fetal exposure to ethanol in the circadian clock functions. This information should help to develop therapeutic strategies in managing sleep-wake disturbances and the resultant health consequences in FAE offspring.

National Institute of Health (NIH)
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Research Project (R01)
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Neurotoxicology and Alcohol Study Section (NAL)
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Grandison, Lindsey
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Rutgers University
Veterinary Sciences
Schools of Earth Sciences/Natur
New Brunswick
United States
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