Effect of ageing on melatonin synthesis induced by 5-hydroxytryptophan and constant light in rats (original) (raw)
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Intake of melatonin increases tryptophan hydroxylase type 1 activity in aged rats: Preliminary study
Experimental Gerontology, 2014
Pineal melatonin is important not only for synchronization of biological rhythms, but also in the ageing process as a potential drug to relieve oxidative damage. During ageing, the nocturnal melatonin production decreases resulting in an increased incidence of disorders. Present in vivo experiments were performed to study the effects of exogenous melatonin chronically administered to old rats on the pineal biosynthesis of melatonin and the precursor serotonin (5-HT) mediated by tryptophan hydroxylase type 1 (TPH-1). Accumulation of 5hydroxytryptophan (5-HTP) after decarboxylase inhibition was used as a measure of the TPH-1 activity. 5-HT and its metabolite 5-HIAA were also quantified by HPLC-ED. As expected, ageing resulted in worsening of different neurochemical parameters. However, chronic intake of melatonin (1 mg/kg/day, diluted in drinking water, 4 weeks) increased TPH-1 activity and significantly improved the age-induced deficits in nocturnal melatonin content in the pineal gland. Results suggest that melatonin intake (or melatonin rich foods) may contribute to recover the pineal function preventing the nocturnal descent of 5-HT and melatonin biosynthesis that normally occur in pineal gland as a consequence of ageing.
The Journal of experimental zoology, 1984
Pineal concentrations of N-acetylserotonin and melatonin and serum levels of melatonin were studied in 3-wk-old (prepubertal), 8-wk-old (adult), and 17-mo-old (senile) male rats. They were adapted to a photoperiod of 12 h light/12 h darkness for a minimum of 1 wk and killed at mid-light and mid-dark. Melatonin and N-acetylserotonin were determined by radioimmunoassay. The concentrations of pineal N-acetylserotonin and melatonin were high in the dark period and low in the light period. Statistical analysis indicated that pineal N-acetylserotonin and melatonin levels per 100 gm body weight declined with age. Similarly, serum melatonin demonstrated diurnal changes in all the age groups studied. In addition, there was a significant reduction in the levels of serum melatonin with age. The parallel patterns of decrease in pineal and serum melatonin levels with age suggest a decline in pineal secretion of melatonin in the older animals.
Experimental gerontology, 1986
Abstracl-Using a semiquantitative immunohistochemical procedure, we have evaluated the 24 hour circadian rhythm of N-acetylserotonin-and melatonin-like immunoreactivity in the retina of male hooded rats that have pigmented eyes. Three and twenty months old Long Evans rats were used. Animals were kept under a 14 light (L): 10 dark (D) lighting cycle and were sacrificed during the month of June. Four time points were assessed in the 24 hour light/dark cycle. Retinal N-acetylserotonin and melatonin were assessed by immunohistochemistry and microphotometric procedures as previously used by us. In young animals, the intensity of retinal N-acetylserotonin and melatonin immunofluorescence was significantly different (P < 0.005, DF = 17) in animals killed during the light vs the dark period with peak values during the dark period. In contrast, retinal N-acetylserotonin and melatonin-immunofluorescence in old animals showed a flattened 24 hour rhythm, with light values as high as those observed during the dark period. The age-associated bluntness of the 24 hour rhythm was more noticeable for N-acetylserotonin than for melatonin immunofluorescence.
Biomedical Journal, 2016
Background: Continuous light or darkness has various effects on different systems. In the present research work, the effects of constant light and darkness exposure of male rats and oral administration of exogenous melatonin on the serum levels of melatonin have been studied. Methods: Thirty adult male Wistar rats were divided into six groups of: (1) Control, (2) melatonin, (3) light, (4) light and melatonin, (5) darkness, and (6) darkness and melatonin. All groups were placed according to light conditions for 10 days. Melatonin was administered orally after a period of 10 days to Groups 2, 4, and 6 (10 mg/kg of body weight). Serum levels of melatonin were measured using ELISA. Results: The results showed the significant difference on serum melatonin in darkness, no light, and control groups. Although serum levels of melatonin were different in melatonin groups, the difference is not significant. Conclusions: We concluded that being exposed to continuous darkness leads to an increase in serum melatonin.
Age-related changes in melatonin synthesis in rat extrapineal tissues
Experimental Gerontology, 2009
In the search of new therapeutic targets improving the quality of life of elderly, melatonin, "the chemical expression of darkness", seems to play a remarkable role in aging process possibly due to its antioxidant, immunoenhancer and antiaging properties.
Responsiveness to melatonin and its receptor expression in the aging circadian clock of mice
American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, 1997
This study determined the effect of age on the efficacy of melatonin treatment to phase shift circadian activity rhythms and on melatonin receptor expression in the suprachiasmatic nucleus (SCN) and paraventricular nucleus of the thalamus (PVNT) of C3H/HeN mice. The circadian rhythm of 2-[125I]iodomelatonin binding, assessed at three times of the day [circadian times (CT) 2, 10, and 18], showed a modest age-related decrease in the SCN but not the PVNT of old C3H/HeN mice (24 mo). There was a tendency for age to reduce Mel1a melatonin receptor mRNA expression in the suprachiasmatic nucleus during the day, but not during the night. The magnitude of phase shifts of circadian activity rhythms (advances or delays) induced by administration of melatonin at CT 10 or CT 2 was identical in young and old C3H/HeN mice. Together, these results suggest that the decrease in melatonin receptor expression in the SCN had little effect on melatonin-induced phase shifts of circadian activity rhythms. ...
Journal of Pineal Research, 2001
Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses Rasmussen DD, Mitton DR, Larsen SA, Yellon SM. Aging-dependent changes in the effect of daily melatonin supplementation on rat metabolic and behavioral responses. J. Pineal Res. 2001; 31:89-94. Abstract: Pineal melatonin secretion has been reported to commonly decrease with aging, whereas intra-abdominal adiposity, plasma insulin and plasma leptin levels tend to increase. We recently demonstrated that daily melatonin administration starting at middle age suppressed male rat intra-abdominal fat, plasma leptin and plasma insulin to youthful levels, suggesting that aging-related changes in pineal melatonin secretion and in energy regulation may be functionally related. Accordingly, we have now investigated the effects of daily melatonin treatment on energy regulation in young versus middle-aged male Sprague -Dawley rats. Addition of melatonin to the drinking water (0.2 mg/mL) produced nocturnal and diurnal plasma melatonin concentrations in middle-aged rats (12 months) equivalent to those of young adult (5 months) rats. Administration of this melatonin dosage every day for 10 wk starting at 10 months of age suppressed (P B 0.01) relative intra-abdominal fat, non-fasted plasma insulin and plasma leptin by 27, 39, and 51%, respectively (vs. vehicle-treated controls). In contrast, administration of melatonin for 10 wk starting at 3 months of age did not significantly alter (P \ 0.10) any of these parameters. The melatonin administration stimulated (102%, PB 0.001) behavioral responsiveness of the middle-aged rats in a test of response to novelty, restoring youthful levels, but did not significantly alter behavioral responsiveness of the young rats. These results suggest that suppression of intra-abdominal adiposity and plasma leptin and insulin levels and stimulation of behavioral responsiveness in response to daily exogenous melatonin begins at middle age, coincident with and likely dependent upon the aging-associated decline in endogenous pineal melatonin secretion. These results further suggest that appropriate melatonin supplementation may potentially provide therapy or prophylaxis not only for the insulin resistance, increased intra-abdominal fat and resulting pathologies that occur with aging, but also for some aging-associated behavioral changes.
Psychoneuroendocrinology, 1993
It has been proposed that aging occurs because of a failure of the pineal gland to produce melatonin from serotonin each day beginning at sunset and throughout the night. This lack leads to a nighttime deficiency of melatonin both absolutely and also relatively to serotonin. As melatonin has widespread integrative and regenerative effects, its lack may lead to disturbances normally associated with aging. The present paper reviews the pertinent literature which appeared since our first publication, but earlier articles are also included. Evidence is presented for a role of melatonin and serotonin in controlling the neuroendocrine and immune networks and in inhibiting the development of ischemic heart and Alzheimer's disease, tumor formation and other degenerative processes associated with aging. The possible role of melatonin in the favourable effects of dietary restriction on aging is also discussed. This paper provides additional evidence that a melatonin deficiency, especially in relation to serotonin, may be responsible for the promotion of aging in the organism.