ABSTRACT
Daniel P. Cardinali UCA-BIOMED-CONICET, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, 1107 Buenos Aires, Argentina
Gregory M. Brown Centre for Addiction and Mental Health, University of Toronto, 100 Stokes St., Toronto, ON M6J 1H4, Canada
Corresponding author: Dr. Daniel P. Cardinali, UCA-BIOMED-CONICET, Faculty of Medical Sciences, Pontificia Universidad Católica Argentina, 1107 Buenos Aires, Argentina. E-mail: danielcardinali@uca.edu.ar, danielcardinali@fibertel.com.ar. Phone: +54911-44743547
ABSTRACT
Normal circadian rhythms are synchronized to a regular 24 h environmental light-dark cycle. Both the suprachiasmatic nucleus (SCN) and melatonin are essential for this adaptation. Melatonin exerts its chronophysiological action in part by acting through specific membrane receptors (MT1, MT2), which have been identified in SCN cells as well as in several neural and non-neural tissues. Both receptors have
been cloned and share general features with other G protein linked receptors. Melatonin also exerts direct effects on intracellular proteins, such as calmodulin or tubulin, has strong free radical scavenger properties, which are non-receptor mediated, is an effective mitochondrial protector and may interact with proteasome to affect intracellular physiology. Within the SCN, melatonin reduces neuronal activity in a time-dependent manner. The disruption of these circadian mechanisms causes a number of sleep disorders known as circadian rhythm sleep disorders (CRSDs). CRSDs include delayed or advanced sleep phase syndromes; non-24 h sleep-wake rhythm disorder, time zone change syndrome (“jet lag”) and shift work sleep disorder. Disturbances in the circadian phase position of plasma melatonin levels have been found in all these disorders. In addition, comorbidity of severe circadian alterations with neurodegenerative diseases like Alzheimer’s disease (AD) has been documented. Currently there is sufficient evidence to implicate endogenous melatonin as an im-
portant mediator in CRSD pathophysiology. The documented efficacy of melatonin to reduce chronic benzodiazepine/Z drug use in insomnia patients is also discussed.
