Journal of pineal research
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There is limited data regarding the effects of melatonin on the activity of neuronal acetylcholine receptors (nAChRs) themselves. This study analyzes the effects of low concentrations of melatonin on nicotine-evoked currents from cerebellar granule neurons (CGNs) in culture. Using electrophysiological and Ca(2+)-imaging techniques, it was found a subset of rat CGNs to which nicotine application elicited both intracellular Ca(2+) transients and inward whole-cell currents. ⋯ The inhibitory effect of melatonin was significantly reduced by luzindole, a competitive antagonist of both MT(1) and MT(2) melatonin receptors. In conclusion, melatonin inhibits nicotinic currents through non-alpha7 heteromeric nAChRs expressed by CGNs in culture, an effect that appears to be at least partially mediated by melatonin membrane receptors. Direct modulation of nicotinic receptors is accomplished at doses that are likely to be physiologically relevant, thus providing a mechanism through which melatonin circadian rhythmic levels could modulate cholinergic activity.
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Controlled Clinical Trial
Long-term effectiveness outcome of melatonin therapy in children with treatment-resistant circadian rhythm sleep disorders.
To date, there have been no prospective long-term studies of melatonin therapy in children. We report here data from a prospective follow-up study of 44 children with neurodevelopmental disabilities and treatment-resistant circadian rhythm sleep disorders (CRSD) who had participated in a placebo controlled, double blind cross-over trial of sustained-release melatonin. The follow-up study involved a structured telephone interview of caregivers every 3 months for upto 3.8 yr. ⋯ At the end of the study, the parental comments regarding the effectiveness of long-term melatonin therapy were highly positive. Parents whose children had sleep maintenance difficulties expressed a wish to have a commercially available controlled-release melatonin product which would promote sleep for 8-10 hr. Hypnotics for children with CRSD should be considered a second line of treatment for those who fail to respond to sleep hygiene and/or melatonin.
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Sleep and circadian disturbances may underlie cognitive dysfunction after major surgery. The aim of this study was to examine the association between sleep and circadian disturbances (as assessed by changes in the melatonin rhythm) and postoperative cognitive dysfunction (POCD). We measured subjective and objective sleep quality, excretion of the major metabolite of melatonin, 6-sulphatoxymelatonin (aMT6s) in urine and cognitive function before and 4 days after major abdominal surgery in 36 patients. ⋯ In conclusion, POCD was associated with worse subjective sleep quality and more awakenings. Circadian rhythmicity as assessed by aMT6s excretion was disturbed after surgery but we were unable to show an association with POCD. Strategies to improve postoperative sleep quality should be investigated in the future.
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We have previously shown that exogenous melatonin improves the preservation of the blood-brain barrier (BBB) and neurovascular unit following cerebral ischemia-reperfusion. Recent evidence indicates that postischemic microglial activation exaggerates the damage to the BBB. Herein, we explored whether melatonin mitigates the cellular inflammatory response after transient focal cerebral ischemia for 90 min in rats. ⋯ This melatonin-mediated decrease in the cellular inflammatory response was accompanied by both reduced brain infarction and improved neurobehavioral outcome by 43% (P < 0.001) and 50% (P < 0.001), respectively. Thus, intravenous administration of melatonin upon reperfusion effectively decreased the emigration of circulatory neutrophils and macrophages/monocytes into the injured brain and inhibited focal microglial activation following cerebral ischemia-reperfusion. The finding demonstrates melatonin's inhibitory ability against the cellular inflammatory response after cerebral ischemia-reperfusion, and further supports its pleuripotent neuroprotective actions suited either as a monotherapy or an add-on to the thrombolytic therapy for ischemic stroke patients.
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Melatonin is a highly effective treatment in different animal models of excitotoxicity or ischemia/reperfusion injury. Due to a lack of patentability, commercial sponsors are not interested in funding clinical evaluations of melatonin. Investigators may initiate small-scale clinical evaluation, and intravenous (i.v.) administration is appropriate in acute stroke patients. ⋯ Gross postmortem examination and histological examination of the brain, kidney, liver and spleen did not reveal any evidence of toxicity. In conclusion, melatonin in propylene glycol markedly elevates plasma levels of melatonin with no serious toxicity. This preparation should be further evaluated in human patients.