Developmental alcohol and circadian clock function

Abstract

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.

Functional components of the internal timekeeping system responsible for the regulation of circadian, or 24-hour, rhythms in mammals. The central circadian pacemaker, or “clock,” is located in the brain in the suprachiasmatic nuclei (SCN). These cells contain the “gears” that are necessary for accurate timekeeping. These gears consist of certain genes (e.g., the Period genes and the Cryptochrome genes) that are rhythmically expressed and regulate ciracadian output pathways. These pathways involve various signals that emanate from the SCN, including neuropeptides, such as brain-derived neurotrophic factor (BDNF), arginine vasopressin (AVP), and vasoactive intestinal polypeptide (VIP). These neuropeptides and other output signals act on other brain regions or peripheral organs and result in the generation of overt rhythms in biochemical, physiological, and behavioral processes throughout the body. The retinohypothalamic tract (RHT) is an entrainment, or input, pathway that mediates the synchronization of the circadian clock to the light-dark cycle.