Fetal Alcohol Exposure and Biological Rhythms

Project: Research project

Description

Prenatal exposure to alcohol has profound effects on the developing nervous system. This can result in neurobehavioral pathology without growth deficits, mental retardation or the dysmorphological characteristics associated with Fetal Alcohol Syndrome (FAS). The effects of fetal alcohol exposure (FAE) are of concern to national health because the FAE population is so much larger that that of FAS. In contrast to FAS, deficits in FAE children can also include changes associated with autonomic and neuroendocrine function. Developmental damage to the suprachiasmatic nucleus (SCN) of the hypothalamus may be a common thread linking many FAE associated neuropathologies. The SCN acts to entrain multiple biological rhythms which normally fluctuate across the 24 hour day. When entrainment is weak or slow to respond to normal entrainment cues such as light, behavioral and physiological disturbances can occur. Preliminary data indicate that fetal alcohol exposure alters adult circadian rhythms in core body temperature and plasma corticosterone. This is accompanied by changes in vasopressin and Per2 expression within the SCN. Vasopressin serves a key effector function of the SCN to modulate amplitude and sensitivity of systems related to the control of rhythms. Per2 is an intrinsic clock gene that is expressed in a circadian fashion within the SCN. Therefore, the experiments described in this application will test the hypothesis that prenatal alcohol exposure disrupts hypothalamic development resulting in a dysregulation of the neural mechanisms involved in the entrainment of autonomic and neuroendocrine rhythms. This application will determine: 1) If FAE causes circadian rhythm dysfunction in adult male and female rats due to an insensitivity of the SCN to photic entrainment. 2) If FAE disrupts the function of local circuits within the SCN that regulate diurnal rhythms of neuropeptides and intrinsic clock genes. 3) If FAE disrupts the functional outputs of the SCN to the paraventricular nucleus of the hypothalamus, a brain region that regulates autonomic and neuroendocrine function. The long term goals of these studies are to establish the extent of rhythm dysregulation caused by FAE and the mechanisms underlying such a dysregulation. This will lay the foundation for future neurodevelopmental studies which will help determine intervention strategies useful in counteracting the effects of FAE on SCN function
StatusFinished
Effective start/end date1/1/0512/31/10

Funding

  • National Institutes of Health: $322,145.00
  • National Institutes of Health: $134,007.00
  • National Institutes of Health: $326,250.00
  • National Institutes of Health: $175,337.00
  • National Institutes of Health: $318,584.00
  • National Institutes of Health: $309,344.00

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Suprachiasmatic Nucleus
Periodicity
Alcohols
Fetal Alcohol Spectrum Disorders
Circadian Rhythm
Vasopressins
Hypothalamus
Paraventricular Hypothalamic Nucleus
Corticosterone
Neuropeptides
Body Temperature
Intellectual Disability
Nervous System
Genes
Cues
Pathology
Light

ASJC

  • Medicine(all)