Light, and melatonin

Mishima K, Okawa M, Hozumi S, Hishikawa Y (2000) Supplementary administration of artificial bright light and melatonin as potent treatment for disorganized circadian rest-activity and dysfunctional autonomic and neuroendocrine systems in institutionalized demented elderly persons. Chronobiol Int 17 419-432... 

Shieh K-R, Chu Y-S, Pan J-T (1997) Circadian change of dopaminergic neuron activity effects of constant light and melatonin. Neuroreport 5 2283-2287. 

May. SAD is also four times more common in women than in men, perhaps because the female hormones of estrogen and progesterone are affected by light and melatonin levels. 

R. F. Riemersma-van der Lek, et al., Effect of Bright Light and Melatonin on Cognitive and Noncognitive Function in Elderly Residents of Group Care Facilities A Randomized Controlled Trial, Journal of the American Medical Association (JAMA) 299 (2008) 2642-2655. 

However, despite its enormous importance to human physiology, no pharmacological compounds targeting the components of the circadian clock system have been identified to date. There are, nevertheless, two therapeutic approaches that are currently used for treatment of circadian-related disorders - full-spectrum and bright light therapy and melatonin therapy. Melatonin is a hormone that is produced by the pineal gland in... 

The rate of melatonin synthesis is controlled primarily by the release of noradrenaline from sympathetic fibres originating in the superior cervical ganglion. The activity of these neurons and, consequently, the synthesis and release of melatonin, follows a circadian rhythm such that sympathetic input and melatonin synthesis are both increased in the dark. This coupling with the light cycle certainly involves the SCN since destruction of this nucleus greatly reduces the fluctuations in melatonin production. Moreover, retrograde transneural tracing has shown that there is a neuronal pathway... 

The precise role of melatonin in sleep and waking is uncertain but it seems to act as a go-between for the light and biological cycles and evidence suggests that it has a reciprocal relationship with the SCN (Fig. 22.3). Its actions are mediated by (MLi) receptors which are found predominantly in the SCN as well as thalamic nuclei and the anterior pituitary. These are G protein-coupled receptors, with seven transmembrane domains, that inhibit adenylyl cyclase. Their activation by melatonin, or an MLi agonist such as 2-iodomelatonin, restores the impaired circadian cycle in aged rats. 

Figure 22.9 Summary of the influence of varying factors on sleep and waking. The EEG is shown diagramatically in the typical arousal (awake) state and in both non-REM (slow wave) and REM sleep. Appropriate activity levels, high or low, are shown for the different factors such as light input, melatonin secretion or ACh, NA, and 5-HT function in the different phases...

Melatonin is found in many areas of many animals. It is involved in the skin coloration of amphibians, and in the thermal or motor regulation in some higher animals. Its major regulatory role is in response to light and, in man, is the major hormone produced by the pineal gland. 

Loss of visual acuity, reduced color vision, and altered light adaptation developed in a 42-year-old woman 2 weeks after she started to take a high protein diet and melatonin 1 mg/day (17). She had also been taking sertraline for the past 4 years. Her vision improved within 2 months of stopping the melatonin and the high protein diet. 

It has been claimed that melatonin contributes significantly to blood serum TAC. Both melatonin and TAC in human serum were found to exhibit the same circadian pattern of changes, with nocturnal peak values at 01 00 hr. Exposure of volunteers to light at night decreased both TAC and melatonin. Removal of melatonin from sera collected at night decreased the TAC value of the samples to basal daytime... 

Circadian variations (mainly due to changes in environmental light) of great amplitude have been described for 5-HT, 5-HIAA and melatonin levels in the pineal body the maximum of 5-HT in the rat pineal gland is 90 ng/gland at noon, the minimum 10 ng/gland around midnight... 

Figure 22.1 Pathways projecting to and from the suprachiasmatic nucleus (SCN). Inputs from photoreceptors in the retina help to reset the circadian clock in response to changes in the light cycle. Other inputs derive from the lateral geniculate complex and the serotonergic, Raphe nuclei and help to reset the SCN in response to non-photic stimuli. Neurons in the SCN project to the hypothalamus, which has a key role in the regulation of the reproductive cycle, mood and the sleep-waking cycle. These neurons also project to the pineal gland which shows rhythmic changes in the rate of synthesis and release of the hormone, melatonin...

Melatonin secretion is synchronized to the light/dark (LD) cycle, with a nocturnal maximum (in young humans, about 200 pg/ml plasma) and low diurnal baseline levels (about 10 pg/ml plasma). Studies have supported the value of the exogenous administration of melatonin in circadian rhythm sleep disorders, insomnia, cancer, neurodegenerative diseases, disorders of the immune function, and oxidative damage (Karasek et al. 2002 Pandi-Perumal et al. 2005, 2006 Srinivasan et al. 2005a,b, 2006 Hardeland et al. 2006). 

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