Academic journal article Alcohol Research

Developmental Alcohol and Circadian Clock Function

Academic journal article Alcohol Research

Developmental Alcohol and Circadian Clock Function

Article excerpt

Studies in rats found that alcohol exposure during the early postnatal period, particularly during the brain-growth-spurt period, can result in cell loss in various brain regions and persistent behavioral impairments. Some investigators have speculated that the body's internal clock, which is located in the suprachiasmatic nuclei (SCN) in the brain, may also be affected by developmental alcohol exposure. For example, alcohol-induced damage to the SCN cells and their function could result in disturbances of the circadian timekeeping function, and these disturbances might contribute to the behavioral impairments and affective disorders observed in people prenatally exposed to alcohol. Preliminary findings of studies conducted in rats suggest that developmental alcohol exposure may indeed interfere with circadian clock function as evidenced by a shortened circadian sleep-wake cycle and changes in the release of certain brain chemicals (i.e., neuropeptides) by SCN cells. KEY WORDS: circadian rhythm; sleep disorde r; fetal alcohol effects; prenatal alcohol exposure; fetal alcohol syndrome; neuropeptides; alcohol-related neurodevelopmental disorder; cytolysis; nerve growth factors; CNS nuclei

Since ancient Roman times, people have suspected that maternal alcohol consumption has deleterious effects on the developing fetus. The dinical diagnosis of fetal alcohol syndrome (FAS), however, was not defined until 1973 when Jones and Smith first documented a constellation of characteristics in the offspring of mothers who had abused alcohol during pregnancy These characteristics include a set of unique facial features, such as a flat groove between the nose and upper lip (i.e., a flat philtrum), a thin upper lip, and a small nose, as well as central nervous system (CNS) dysfunction. The CNS defects--which include reduced brain size (i.e., microencephaly), reductions in the volume of various brain regions (e.g., in the anterior cerebellum [1] and the corpus callosum [2]) and behavioral impairments (e.g., learning difficulties and attention deficits) (Roebuck et al. 1999)--are by far the most debilitating features associated with FAS (Stratton et al. 1996).

During the past 20 years, studies using animal model systems have generated substantial information on the risk factors associated with maternal alcohol use and the spectrum of alcohol-induced brain injuries among affected offspring. Perhaps most importantly, these animal studies have identified the brain-growth-spurt period as the developmental stage most vulnerable to alcohol-induced brain injury. In humans, this particular brain-growth period begins during the third trimester of pregnancy, peaks around birth, and persists through the first few years of life. In rats, which are the most commonly used species in fetal alcohol research, the corresponding rapid brain-growth period occurs during the first 2 weeks after birth.

Alcohol exposure in rats during this early postnatal period produces structural changes in the brain comparable to those observed in human FAS patients. These changes range from reductions in the rat's brain size and weight (Maier et al. 1996) to the loss of various cell populations in discrete brain regions, such as the cerebellum and the hippocampus [3] (Bonthius and West 1990). In addition to these structural changes, developmental alcohol exposure induces a wide spectrum of neurochemical changes in the developing rat brain (Manteuffel 1996).

One key question in the fetal alcohol research field is whether developmental alcohol exposure has long-term consequences. In humans, the characteristic facial abnormalities associated with FAS typically become less prominent with age. However, many reported findings suggest that alcohol-induced deficits in brain development may persist into adulthood. Using noninvasive techniques (e.g., magnetic resonance imaging and positron emission tomography) in a small number of children with FAS, researchers have confirmed brain damage from prenatal alcohol exposure and have determined the related behavioral consequences, including learning deficits, hyperactivity, lack of inhibition, depression, and sleep disturbances (Hannigan et al. …

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