It is estimated that 2,000-12,000 babies are born each year with fetal alcohol syndrome (FAS) (Stratton et al., 1996). By far the most debilitating feature of FAS in CNS dysfunction that results from structure are known to persist into adulthood. However, information on the long-term neurobehavioral correlates of this alcohol-related brain damage is limited. The circadian regulation of most body processes by the clock in the suprachiasmatic nucleus (SCN) represents an area in which limited information is available on the consequences of developmental alcohol exposure in humans or animal models. Offspring exposed to heavy maternal alcohol consumption during pregnancy have been reported to show disturbances in their sleep-wake patterns (Rosett et al., 1979). Consistent with this finding, our PRELIMINARY STUDIES demonstrate that alcohol exposure during the third trimester equivalent in rats produces permanent changes in the circadian rhythm of activity. Therefore, experiments in this proposal will utilize multidisciplinary approaches to examine the long-term effects of three different alcohol doses on the circadian rhythm of activity on the anatomical, cellular and molecular organization of the SCN clock. The patterns of wheel- running behavior in adult rats will be assessed for alcohol-related changes in fundamental properties such as circadian period and rhythm amplitude. Subsequent to this behavioral analysis, the SCN will be evaluated for evidence of general cell loss and perturbations in its rhythmic expression of the putative clock genes, Perl, Per2 and Cry2, and the output signals, vasopressin (AVP), vasoactive intestinal polypeptide (VIP) and brain-derived neurotrophic factor (BDNF). Unlike CNS involvement in the neural regulation of most other behaviors, the discrete localization of circadian clock function to the SCN provides a unique opportunity to identify cellular and molecular correlates of alcohol-related neurobehavioral disturbances. By determining how the SCN and its circadian function are affected by developmental alcohol exposure, these studies are expected to yield important information on the basic mechanisms underlying alcohol-induced brain injury during development. Such information could lead to new strategies in the treatment of known behavioral correlates of FAS related to sleep problems and to mental and physical disorders associated with sleep-wake abnormalities.

Agency
National Institute of Health (NIH)
Institute
National Institute on Alcohol Abuse and Alcoholism (NIAAA)
Type
Research Project (R01)
Project #
5R01AA013242-05
Application #
6879976
Study Section
Special Emphasis Panel (ZAA1-BB (03))
Program Officer
Grandison, Lindsey
Project Start
2001-07-01
Project End
2007-03-31
Budget Start
2005-04-01
Budget End
2007-03-31
Support Year
5
Fiscal Year
2005
Total Cost
$216,000
Indirect Cost
Name
Texas A&M University
Department
Anatomy/Cell Biology
Type
Schools of Medicine
DUNS #
835607441
City
College Station
State
TX
Country
United States
Zip Code
77845
Farnell, Yuhua Z; Allen, Gregg C; Neuendorff, Nichole et al. (2009) Effects of neonatal alcohol exposure on vasoactive intestinal polypeptide neurons in the rat suprachiasmatic nucleus. Alcohol 43:387-96
Farnell, Yuhua Z; Allen, Gregg C; Nahm, Sang-Soep et al. (2008) Neonatal alcohol exposure differentially alters clock gene oscillations within the suprachiasmatic nucleus, cerebellum, and liver of adult rats. Alcohol Clin Exp Res 32:544-52
Allen, Gregg C; West, James R; Chen, Wei-Jung A et al. (2005) Neonatal alcohol exposure permanently disrupts the circadian properties and photic entrainment of the activity rhythm in adult rats. Alcohol Clin Exp Res 29:1845-52
Allen, Gregg C; Farnell, Yuhua Z; Maeng, Ji-ung et al. (2005) Long-term effects of neonatal alcohol exposure on photic reentrainment and phase-shifting responses of the activity rhythm in adult rats. Alcohol 37:79-88
Allen, Gregg C; West, James R; Chen, Wei-Jung A et al. (2004) Developmental alcohol exposure disrupts circadian regulation of BDNF in the rat suprachiasmatic nucleus. Neurotoxicol Teratol 26:353-8
Farnell, Yuhua Z; West, James R; Chen, Wei-Jung A et al. (2004) Developmental alcohol exposure alters light-induced phase shifts of the circadian activity rhythm in rats. Alcohol Clin Exp Res 28:1020-7