[Effects of ethanol on the development of circadian time keeping system]

Abstract

Ethanol exposure during gestation can have devastating consequences on the developing organism. Children who have a history of prenatally exposure to ethanol may show morphological and functional alterations, referred to as fetal alcohol spectrum disorders (FASD). Fetal alcohol syndrome (FAS), which is characterized by pre- and postnatal growth deficiency, specific cranial/facial features, and dysfunction of central nervous system, is the most severe end of FASD. FAS or FASD children are known to suffer from disturbance of sleep and/or food intake behaviors. These neuropsychiatric symptoms may be due to impairment of the system regulating circadian rhythms. Recently, animal studies revealed that ethanol exposure during brain development can cause alterations in the circadian rhythm and its regulating system. We examined the effects of pre- or postnatal exposure to ethanol on the circadian rhythm in adulthood by measuring deep body temperature and wheel running activity in rats. After a phase delay in the light/dark cycle, ethanol-exposed rats took longer than control rats to resynchronize to the new light/dark cycle. These results suggest that both pre- and postnatal ethanol exposure impair the development of the circadian clock response to light cue. Because abnormal development of the circadian clock system might contribute to the neuropsychiatric symptoms seen in FASD, it is believed that normalizing the disturbed rhythm improves the symptoms. However, the mechanisms of dysfunction and potential interventions for disturbance of circadian clock system still remain to be elucidated. Further investigations are required to fully understand long-term effects of ethanol on the development of circadian rhythms.