Prenatal Alcohol Exposure Can Alter Circadian Rhythms In Offspring

"Human infants with FASD may suffer from sleep disorders, including a reduced amount of sleep, abnormal brain wave activity, and fragmented rapid eye movement and slow-wave sleep, which may be related, in part, to circadian dysregulation," explained Jennifer D. Thomas, associate professor of psychology at San Diego State University and corresponding author for the study. "Disruptions in circadian rhythms can also influence other behaviors, including attention and mood regulation. In fact, individuals with FASD may suffer from depression and other psychopathologies." Although sleeping, eating and mood can be influenced by many factors, she said, the circadian systems are responsible for coordinating multiple physiological systems with environmental cues.

"Most of our body processes are regulated in the circadian fashion," concurred David Earnest, a professor in the department of neuroscience and experimental therapeutics at Texas A&M University Health Sciences Center. "We know that these circadian rhythms are important in human health, although we still need to fully determine how alterations in circadian rhythmicity are linked to human mental and physical disorders."

For this study, researchers exposed male Sprague-Dawley rats to 6.0 g/kg of alcohol per day (n = 8), using an artificial rearing procedure, from postnatal days four through nine. The alcohol level represented heavy binge drinking. An artificially reared control group (n = 8) and a normally reared control group (n = 8) were also included in the study design. At 10 to 12 weeks of age, wheel-running behavior was continuously measured for eight days under a 12-hour light/12-hour dark (LD) cycle. Then the cycle was delayed by six hours and the rats were exposed to a new LD cycle for an additional six days. Their adjustment to the new cycle was evaluated.

"Our study demonstrated that exposure to alcohol during the third trimester, when components of the circadian system in the brain are developing, can lead to long-lasting alterations in the ability to entrain the cycles to environmental cues, like light/dark cycle," said Thomas. "These data suggest that dysfunction of circadian systems may contribute to some of the behavioral problems observed in children with FASD."

"This is the equivalent to a person undergoing exposure to 'jet lag,'" noted Earnest. "Basically, if you take a human and go across a number of time zones from east to west, similar to the light/dark cycle of these animals, some people will shift quickly, and some will not, and may even experience some physical problems or illness because of effects on their immune system. The responses of the alcohol-treated animals indicated that they resynchronized to the shifted light/dark cycle more slowly than the control animals."

The implications of these results for humans, added Earnest, are much broader than the term "jet lag" might indicate. "These individuals are going to have difficulties, in terms of their ability to function, while traveling across time zones and also during shift work," he said. "There are a couple of prominent examples in history regarding this: the Exxon Valdez and Chernobyl. The captain of the Exxon Valdez was not only working shift work, but he was drinking too, and unable to maintain a normal, necessary performance. With Chernobyl, the shift-work schedules were inappropriate and, at the time that the accident happened, poor mental and physical performances contributed to the disaster."

The underlying message, said Thomas, is that drinking alcohol during pregnancy can have long-lasting damaging effects to the offspring. "There is currently no known safe amount of alcohol that can be consumed during pregnancy, so it is best to abstain from alcohol drinking during pregnancy. We need to better understand the mechanisms of this dysfunction to determine if there are ways to mitigate the circadian dysfunction and behavioral dysregulation associated with developmental alcohol exposure."

Alcoholism: Clinical & Experimental Research (ACER) is the official journal of the Research Society on Alcoholism and the International Society for Biomedical Research on Alcoholism. Co-authors of the ACER paper, "Alterations in Circadian Rhythm Phase Shifting Ability in Rats Following Ethanol Exposure During the Third Trimester Brain Growth Spurt," were: Hiromi Sakata-Haga of the Center for Behavioral Teratology in the Department of Psychology at San Diego State University, and the Department of Anatomy and Developmental Neurobiology in the Institute of Health Biosciences at the University of Tokushima Graduate School; Hector D. Dominguez and Edward P. Riley of the Center for Behavioral Teratology in the Department of Psychology at San Diego State University; Hiroyoshi Sei of the Department of Integrated Physiology in the Institute of Health Biosciences at the University of Tokushima Graduate School; and Yoshihiro Fukui of the Department of Anatomy and Developmental Neurobiology in the Institute of Health Biosciences at the University of Tokushima Graduate School. The study was funded by the National Institute on Alcohol Abuse and Alcoholism, and the Japan Society for the Promotion of Science.