MELATONIN RECEPTORS IN AGING SUPRACHIASMATIC NUCLEUS

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Disruption of sleep and circadian rhythms occurs with aging. Misalignment between the phase of the circadian timing system and habitual bedtime appears to be a major factors contributing to this disruption. A treatment producing improvement in sleep quality and circadian organization in the elderly would have a significant, positive impact on the health and welfare on this growing segment of our population. One avenue of treatment involves timed administration of the pineal hormone, melatonin. Melatonin administration improves sleep in young people. It has been proposed that the sleep promoting effects of melatonin. Melatonin administration improves sleep in young people. It has been proposed that the sleep-promoting effects of melatonin are due to melatonin's ability to silence a wide-promoting signal generated by the biological clock in the suprachiasmatic nuclei (SCN) of the hypothalamus. The use of melatonin as a treatment for aging-related insomnia requires that the aging brain, and particularly the aging SCN, retains sensitivity to melatonin. Studies in the current project will assess sensitivity of the aging SCN to melatonin,a nd will investigate the mechanisms of melatonin action in the SCN. Specifically, the density of melatonin receptors in the human SCN will e studied as a function of age, using brain specimens collected at autopsy. An animal model will be used to study alterations in melatonin efficacy in influencing SCN function in aging. Developmental- and age-related alterations in melatonin receptors in the mouse SCN will be demonstrated, followed by examination of the ability of melatonin to suppress SCN electrical activity as a function of age and melatonin receptor density. The interaction of melatonin with other agents capable of resetting the SCN circadian clock, and the mechanisms by which melatonin alters electrical activity will be examined in vitro. These studies will determine whether the aging brain retains sensitivity to melatonin, and thus are a necessary part of the overall objective of assessing the potential of melatonin to treat sleep and circadian disorders in the elderly.