Alcohol exposure in utero, even at doses that are not overtly teratogenic, persists as a major medical problem in this country. This proposal will establish both the mechanism and consequences of alcohol-induced damage to thermoregulation. An alcohol-exposed infant with body temperature disturbances is an infant at greater risk for respiratory distress, sudden infant death syndrome, and delayed neural growth. This alcohol-exposed infant may also be less responsive and thus may not be able to elicit adequate parental care as well as a non-exposed newborn. The alcohol- exposed newborn may need special care in terms of thermoregulation; a premature or low birth weight infant would be particularly at risk. This application will investigate the effects of prenatal alcohol exposure on the development of thermogenesis in brown adipose tissue, the primary means of heat production in infants. To determine how prenatal alcohol exposure alters the normal developmental course of sympathetic nervous system control of brown adipose tissue thermogenesis, this grant will examine the effects of prenatal alcohol exposure on the responsiveness of adrenergic receptors and the expression of ~3-adrenergic receptor mRNA in brown adipose tissue. Since the local production of thyroid hormone in brown adipose tissue also appears to be critical for thermogenesis, this grant will investigate the effects of prenatal alcohol exposure on the gestational surge in thyroid hormone production, when it functions as a developmental factor, and the postnatal production of thyroid hormone, when it functions as a """"""""permissive"""""""" agent to maximize tissue response to norepinephrine. Finally, this grant will determine whether the effects of prenatal alcohol exposure on control of brown adipose tissue function have longterm consequences in adult offspring. Brown adipose tissue thermogenesis is """"""""recruited"""""""" under two conditions that are physiologically stressful: high fat, high carbohydrate diets, and chronic exposure to cold. This grant will elucidate the effects of prenatal alcohol exposure on sympathetic nervous system regulation of diet-induced thermogenesis and cold-induced thermogenesis in brown adipose tissue of adult offspring, and determine if there are sex differences in response to these stressors. Since the early postpartum days represent an optimal intervention period, the information gained in this proposal will be of great value for early treatment and intervention. The studies on adult offspring will provide information about FAE populations at special risk: Native American living in northern climates, Alaskan Native Americans and older affected offspring with high fat/high carbohydrate diets.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA008605-06
Application #
2389882
Study Section
Biochemistry, Physiology and Medicine Subcommittee (ALCB)
Project Start
1991-04-01
Project End
1999-03-31
Budget Start
1997-04-01
Budget End
1999-03-31
Support Year
6
Fiscal Year
1997
Total Cost
Indirect Cost
Name
Williams College
Department
Psychology
Type
Schools of Arts and Sciences
DUNS #
City
Williamstown
State
MA
Country
United States
Zip Code
01267
Zimmerberg, Betty; Weston, Heather E (2002) Postnatal stress of early weaning exacerbates behavioral outcome in prenatal alcohol-exposed juvenile rats. Pharmacol Biochem Behav 73:45-52
Zimmerberg, B; Rackow, S H; George-Friedman, K P (1999) Sex-dependent behavioral effects of the neurosteroid allopregnanolone (3alpha,5alpha-THP) in neonatal and adult rats after postnatal stress. Pharmacol Biochem Behav 64:717-24
Zimmerberg, B; Blaskey, L G (1998) Prenatal stress effects are partially ameliorated by prenatal administration of the neurosteroid allopregnanolone. Pharmacol Biochem Behav 59:819-27
Zimmerberg, B; Brown, R C (1998) Prenatal experience and postnatal stress modulate the adult neurosteroid and catecholaminergic stress responses. Int J Dev Neurosci 16:217-28
Zimmerberg, B; McDonald, B C (1996) Prenatal alcohol exposure influences the effects of neuroactive steroids on separation-induced ultrasonic vocalizations in rat pups. Pharmacol Biochem Behav 55:541-7
Zimmerberg, B; Drucker, P C; Weider, J M (1995) Differential behavioral effects of the neuroactive steroid allopregnanolone on neonatal rats prenatally exposed to alcohol. Pharmacol Biochem Behav 51:463-8
Zimmerberg, B; Smith, C D; Weider, J M et al. (1995) The development of beta 1-adrenoceptors in brown adipose tissue following prenatal alcohol exposure. Alcohol 12:71-7
Zimmerberg, B; Brunelli, S A; Hofer, M A (1994) Reduction of rat pup ultrasonic vocalizations by the neuroactive steroid allopregnanolone. Pharmacol Biochem Behav 47:735-8
Zimmerberg, B; Brown, A P; Lee, H H et al. (1993) Effects of prenatal alcohol exposure on uncoupling protein in brown adipose tissue in neonatal rats. Alcohol 10:149-53
Zimmerberg, B; Tomlinson, T M; Glaser, J et al. (1993) Effects of prenatal alcohol exposure on the developmental pattern of temperature preference in a thermocline. Alcohol 10:403-8

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