Suprachiasmatic nucleus and melatonin

Abstract

AA-NAT= : aryl alkylamine N-acetyltransferase; AD= : Alzheimer disease; AVP= : arginine vasopressin; Ca2+= : calcium; CaMK= : calmodulin kinase; cAMP= : cyclic adenosine monophosphate; CREB= : cyclic adenosine monophosphate (cAMP) responsive element binding protein; GABA= : γ-aminobutyric acid; HI-OMT= : hydroxyl indol-O-methyltransferase; 5-HTP= : 5-hydroxytryptophan; IML= : intermediolateral cell column; MT= : melatonin; NE= : norepinephrine; NO= : nitric oxide; PAC2= : pituitary adenylate cyclase activating polypeptide receptor 2; PCACP= : pituitary adenylate cyclase activating polypeptide; PKA= : protein kinase A; PVN= : paraventricular nucleus; RAI1 = : retinoic acid induced gene 1; RHT= : retinohypothalamic tract; SCG= : superior cervical ganglion; SCN= : suprachiasmatic nucleus. Melatonin is a ubiquitous molecule that has a major role in regulation of sleep and other cyclical bodily activities. The suprachiasmatic nucleus contains neurons that exhibit a circadian pattern of activity and regulate melatonin secretion by the pineal gland in response to the environmental light/dark cycle. Melatonin signals both the time of the day (a “clock” function) and the time of the year (a “calendar” function) to all tissues of the body. Recent evidence indicates that abnormalities in the circadian control of melatonin secretion may have an important role in sleep disorders associated with aging, Alzheimer disease, and other degenerative and developmental disorders. Because of its antioxidant properties, melatonin may also have potential neuroprotective effects. There are several recent reviews on the mechanisms controlling circadian rhythms and melatonin secretion and functions.1–9 ### Suprachiasmatic nucleus activity and its entrainment by light. The suprachiasmatic nucleus (SCN) of the anterior hypothalamus is the master clock controlling circadian rhythms in mammals.1–3 The SCN neurons have a near-24-hour rhythm of electrical activity, even in the absence of environmental cues. This circadian activity reflects the rhythmic pattern of expression of core genes, called clock genes, that are regulated transcriptionally, translationally, and post-translationally by autoregulatory feedback loops.1–3 The circadian influences of SCN neurons are distributed throughout different target organs of the body by efferent neural and humoral signals, particularly circulating melatonin. The SCN controls melatonin secretion via a multisynaptic pathway1,6 (figure 1). Figure 1 Pathway involving entrainment of melatonin secretion by light The circadian regulation of melatonin secretion depends on an indirect pathway that originates from photosensitive ganglion cells of the retina and reaches, via the retinohypothalamic tract to the suprachiasmatic nucleus, which is the circadian pacemaker. The suprachiasmatic nucleus, via an inhibitory projection to the paraventricular nucleus of the hypothalamus, controls the sympathetic output to the pineal gland that is …