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Endogenous Melatonin (endogenous + melatonin)
Selected AbstractsEndogenous melatonin protects L -DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L -DOPA therapy in Parkinson's diseaseJOURNAL OF PINEAL RESEARCH, Issue 3 2006Gaia Rocchitta Abstract:, We previously showed, using microdialysis, that autoxidation of exogenous L-dihydroxyphenylalanine (l -DOPA) occurs in vivo in the extracellular compartment of the freely moving rat, with a consequent formation of l -DOPA semiquinone (l -DOPA-SQ). In the present study, intrastriatal infusion of l -DOPA (1.0 ,m for 200 min) increased dialysate l -DOPA concentrations (maximum increases up to 116-fold baseline values); moreover, l -DOPA-SQ was detected in dialysates. Individual dialysate concentrations of l -DOPA were negatively correlated with those of l -DOPA-SQ. Co-infusion of N -acetylcysteine (100 ,m) or melatonin (50 ,m) increased l -DOPA (up to 151- and 246-fold, respectively) and decreased l -DOPA-SQ (by about 53% and 87%, respectively) dialysate concentrations. Systemic l -DOPA [25 mg/kg intraperitoneally (i.p.) twice in a 12-h interval] significantly increased striatal baseline dialysate concentrations of l -DOPA and decreased dopamine (DA) and ascorbic acid (AsAc) concentrations, when compared with controls. Following systemic l -DOPA, l -DOPA-SQ was detected in dialysates. Endogenous melatonin was depleted in rats maintained on a 24-h light cycle for 1 wk. In melatonin-depleted rats, systemic l -DOPA induced a smaller increase in dialysate l -DOPA, a greater increase in l -DOPA-SQ formation, and a greater reduction in DA and AsAc dialysate concentrations. Co-administration of melatonin (5.0 mg/kg, i.p., twice in a 12-h interval) with l -DOPA, in control as well as in light-exposed rats, significantly increased dialysate l -DOPA concentrations, greatly inhibited l -DOPA-SQ formation, and restored up to the control values dialysate DA and AsAc concentrations. These findings demonstrate that endogenous melatonin protects exogenous l -DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co-administration of melatonin with l -DOPA markedly increases striatal l -DOPA bioavailability in control as well as in melatonin-depleted rats. These results may be of relevance to the long-term l -DOPA therapy of Parkinson's disease. [source] The relationship between melatonin and cortisol rhythms: clinical implications of melatonin therapyDRUG DEVELOPMENT RESEARCH, Issue 3 2005N. Zisapel Abstract Disturbances in circadian rhythm have been linked to chronic diseases such as insomnia, hypertension, diabetes, and depression. Here we review recent studies on the age-related changes in cortisol and melatonin rhythms and then present descriptive statistics on our preliminary findings on the rectification of the cortisol rhythms by melatonin therapy in elderly patients with insomnia. In adults, the melatonin onset typically occurs during low cortisol secretion. Administration of exogenous melatonin around dusk will shift the phase of the human circadian clock to earlier hours (advance phase shift) leading to phase advances in circadian rhythms (e.g., sleep, endogenous melatonin, cortisol). With aging, the production of melatonin declines and is shifted to later hours while the production of cortisol increases and its peak occurs earlier in the night. In a randomized placebo-controlled crossover study with 8 patients with insomnia aged 55 years and older, a group characterized by low and delayed melatonin production, administration of prolonged-release melatonin in the evening was able to rectify the early onset cortisol production. This delay in nocturnal cortisol onset may explain in part the improvement in sleep quality in elderly patients with insomnia, in schizophrenics, and in depressed patients. Support of circadian pacemaker function by melatonin may provide a new strategy in the treatment of disorders related to impairments in the internal temporal order. The clinical benefit from a decrease in cortisol during the early part of the night may lie beyond the improvement of sleep into a better control of blood pressure, metabolism, and mood. Drug Dev. Res. 65:119,125, 2005. © 2005 Wiley-Liss, Inc. [source] Photic Regulation of mt1 Melatonin Receptors in the Siberian Hamster Pars Tuberalis and Suprachiasmatic Nuclei: Involvement of the Circadian Clock and Intergeniculate LeafletJOURNAL OF NEUROENDOCRINOLOGY, Issue 3 2000Schuster In the Siberian hamster suprachiasmatic nuclei and pars tuberalis of the pituitary, high affinity mt1 melatonin receptors are present. We have previously shown that night applied light pulse induced an increase in mt1 mRNA expression in the suprachiasmatic nuclei of this species, independently of the endogenous melatonin. Here, we report the photic regulation of melatonin receptor density and mRNA expression in the suprachiasmatic nuclei and pars tuberalis of pinealectomized Siberian hamsters and the implication in this control of either the circadian clock or the intergeniculate leaflet. The results show that: (1) A 1-h light pulse, delivered during the night, induces a transitory increase in mt1 mRNA expression in the suprachiasmatic nuclei and pars tuberalis. After 3 h this increase has totally disappeared (suprachiasmatic nuclei) or is greatly reduced (pars tuberalis). (2) The melatonin receptor density, in the suprachiasmatic nuclei, is not affected by 1 or 3 h of light, while it is strongly increased in the pars tuberalis. (3) In hamsters kept in constant darkness, the mt1 mRNA rise is gated to the subjective night in the suprachiasmatic nuclei and pars tuberalis. In contrast, the light-induced increase in melatonin binding is also observed in the subjective day in the pars tuberalis. (4) intergeniculate leaflet lesion totally inhibits the mt1 mRNA expression rise in the suprachiasmatic nuclei, while it has no effect on the light-induced increase in mt1 mRNA in the pars tuberalis. However, the light-induced increase in melatonin receptor density is totally prevented by the intergeniculate leaflet lesion in the pars tuberalis. These results show that: (1) the photic regulations of mt1 mRNA expression and receptor density are independent of each other in both the suprachiasmatic nuclei and pars tuberalis; and (2) the circadian clock and the intergeniculate leaflet are implicated in the photic regulation of melatonin receptors but their level of action differs totally between the suprachiasmatic nuclei and pars tuberalis. [source] Endogenous melatonin protects L -DOPA from autoxidation in the striatal extracellular compartment of the freely moving rat: potential implication for long-term L -DOPA therapy in Parkinson's diseaseJOURNAL OF PINEAL RESEARCH, Issue 3 2006Gaia Rocchitta Abstract:, We previously showed, using microdialysis, that autoxidation of exogenous L-dihydroxyphenylalanine (l -DOPA) occurs in vivo in the extracellular compartment of the freely moving rat, with a consequent formation of l -DOPA semiquinone (l -DOPA-SQ). In the present study, intrastriatal infusion of l -DOPA (1.0 ,m for 200 min) increased dialysate l -DOPA concentrations (maximum increases up to 116-fold baseline values); moreover, l -DOPA-SQ was detected in dialysates. Individual dialysate concentrations of l -DOPA were negatively correlated with those of l -DOPA-SQ. Co-infusion of N -acetylcysteine (100 ,m) or melatonin (50 ,m) increased l -DOPA (up to 151- and 246-fold, respectively) and decreased l -DOPA-SQ (by about 53% and 87%, respectively) dialysate concentrations. Systemic l -DOPA [25 mg/kg intraperitoneally (i.p.) twice in a 12-h interval] significantly increased striatal baseline dialysate concentrations of l -DOPA and decreased dopamine (DA) and ascorbic acid (AsAc) concentrations, when compared with controls. Following systemic l -DOPA, l -DOPA-SQ was detected in dialysates. Endogenous melatonin was depleted in rats maintained on a 24-h light cycle for 1 wk. In melatonin-depleted rats, systemic l -DOPA induced a smaller increase in dialysate l -DOPA, a greater increase in l -DOPA-SQ formation, and a greater reduction in DA and AsAc dialysate concentrations. Co-administration of melatonin (5.0 mg/kg, i.p., twice in a 12-h interval) with l -DOPA, in control as well as in light-exposed rats, significantly increased dialysate l -DOPA concentrations, greatly inhibited l -DOPA-SQ formation, and restored up to the control values dialysate DA and AsAc concentrations. These findings demonstrate that endogenous melatonin protects exogenous l -DOPA from autoxidation in the extracellular compartment of the striatum of freely moving rats; moreover, systemic co-administration of melatonin with l -DOPA markedly increases striatal l -DOPA bioavailability in control as well as in melatonin-depleted rats. These results may be of relevance to the long-term l -DOPA therapy of Parkinson's disease. [source] Dietary supplementation with melatonin reduces levels of amyloid beta-peptides in the murine cerebral cortexJOURNAL OF PINEAL RESEARCH, Issue 4 2004Debomoy K. Lahiri Abstract:, Melatonin levels decrease with aging in mice. Dietary supplementation with melatonin has recently been shown to result in a significant rise in levels of endogenous melatonin in the serum and all other tissue samples tested. Herein, the effects of dietary melatonin on brain levels of nitric oxide synthase, synaptic proteins and amyloid beta-peptides (A,) were determined in mice. Melatonin supplementation did not significantly change cerebral cortical levels of nitric oxide synthase or synaptic proteins such as synaptophysin and SNAP-25. Increased brain melatonin concentrations however, led to a significant reduction in levels of toxic cortical A, of both short and long forms which are involved in amyloid depositions and plaque formation in Alzheimer's diseases. Thus, melatonin supplementation may retard neurodegenerative changes associated with brain aging. Depletion of melatonin in the brain of aging mice may in part account for this adverse change. [source] Stimulatory and entraining effect of melatonin on tuberoinfundibular dopaminergic neuron activity and inhibition on prolactin secretionJOURNAL OF PINEAL RESEARCH, Issue 4 2000Yeh-Shiu Chu The aims of the present study were to determine if melatonin exerts an effect on prolactin (PRL) secretion via the tuberoinfundibular dopaminergic (TIDA) neurons and if endogenous or exogenous melatonin has an entraining effect on the rhythmic changes of TIDA neuronal activity and PRL secretion. Melatonin given in the morning (10:00 h), dose- (0.01,1 mg/kg, ip) and time- (at 15 and 60 min, but not at 30 min) dependently stimulated TIDA neuronal activity in ovariectomized (OVX), estrogen-treated rats as determined by 3,4-dihydroxyphenylacetic acid (DOPAC) levels in the median eminence (ME). Serum PRL was concurrently inhibited by the injection. Melatonin administered in the afternoon (15:00 h) was even more effective in stimulating the lowered TIDA neuronal activity and inhibiting the increased PRL level than that given in the morning (10:00 h). S-20098, a melatonin agonist was also effective in stimulating the TIDA neurons. In contrast, S-20928, a putative melatonin antagonist, while it had no effect by itself, blocked the effect of S-20098. Although S-20928 failed to prevent melatonin's effect on ME DOPAC levels, six interspaced injections of S-20928, from 18:00 to 01:30 h, significantly blocked the increase of ME DOPAC levels at 03:00 h, indicating that the endogenous melatonin may play a role. We further used rats that received daily injection of melatonin (1 mg/kg, ip) at 18:00 h for 10 days and found that the injection augmented basal TIDA neuronal activity at 11:00 h and blunted the afternoon PRL surge. In all, melatonin can have an inhibitory effect on PRL secretion by stimulating the TIDA neurons, and it may help to entrain the circadian rhythms of both TIDA neuronal activity and PRL secretion. [source] Direct determination of endogenous melatonin in human saliva by column-switching semi-microcolumn liquid chromatography/mass spectrometry with on-line analyte enrichmentRAPID COMMUNICATIONS IN MASS SPECTROMETRY, Issue 12 2004Akira Motoyama An analytical method that enables direct and sensitive determination of endogenous melatonin (MLT) in human saliva was developed by means of column-switching semi-microcolumn liquid chromatography (i.d.: 1,2,mm)/mass spectrometry (LC/MS). The system allows direct injection analysis of a 400-,L aliquot of saliva with minimal sample pretreatment (internal standard (IS) addition and vortex mixing) and a relatively short run-time (10,min). The system consists of three columns to attain large volume injection and on-line analyte enrichment. A pre-column packed with a silica-based mixed-functional C8 (4.0,mm i.d.,×,20,mm) was used for on-line sample cleanup. MLT and an IS, the d7 isomer of MLT (d7-MLT), were heart-cut by valve switching and enriched at the top of the intermediate trapping column packed with a silica-based C18 (4.0,mm i.d.,×,10,mm). Subsequently, the analytes were backflushed into a semi-micro C18 silica column (2.0,mm i.d.,×,150 mm) for the final separation. MLT and IS were ascertained by positive electrospray ionization and selected ion monitoring (SIM). MLT was monitored based on its fragment ion at m/z 174.1 by in-source collision-induced dissociation (CID). The validation of this method revealed a detection limit of 2.5,pg,mL,1 at a signal-to-noise (S/N) ratio of 5. The linearity of the method was established in the ranges 5,250 and 100,2500,pg,mL,1 with a coefficient of determination of greater than 0.998. Accuracies, evaluated at five levels in the range 5,1000,pg,mL,1, were between 81 and 108% with a relative standard deviation (RSD) ranging from 1.3,20%. The method was successfully applied for the endogenous saliva MLT monitoring of two healthy subjects. Copyright © 2004 John Wiley & Sons, Ltd. [source] | ||||||||||