Melatonin has differential effects on age-induced stoichiometric changes in daily chronomics of serotonin metabolism in SCN of male Wistar rats

Dec 17, 2014Biogerontology

Melatonin affects daily serotonin metabolism changes with aging in the brain’s internal clock of male rats

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Abstract

Aging in male rats results in a significant decrease in mean levels of melatonin and related metabolites in the suprachiasmatic nucleus.

Mean levels of several serotonin metabolic components, including melatonin and N-acetylserotonin, decrease with age.
Conversely, levels of tryptophan and its derivatives increase in aged rats.
Daily fluctuations in metabolites of serotonin metabolism diminish significantly with aging.
Age-related changes in the interaction of serotonin components are noted by middle age and continue to evolve into later years.
Melatonin administration appears to restore some ratios of serotonin metabolites altered by aging.

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Suprachiasmatic nucleus (SCN) controls various physiological, endocrine and behavioral functions by regulating conversion of serotonin (5-HT) to melatonin (MEL). Aging leads to alterations in the neural and temporal organization of the SCN leading to circadian dysfunction. Age-induced stoichiometric alterations in daily chronomics of various components of 5-HT metabolism were studied by constructing interactomes between parameters. The levels of tryptophan (TRP), 5-hydroxytryptophan (5-HTP), 5-hydroxytryptamine (5-HT), N-acetylserotonin (NAS), N-acetyl 5-methoxytryptamine (MEL), 5-hydroxyindoleacetic acid (5-HIAA), 5-methoxyindole acetic acid (5-MIAA), 5-hydroxytryptophol (5-HTOH), 5-methoxytryptophol (5-MTOH) and N-acetyltryptamine (NAT) were measured at (Zeitgeber time 0, 6, 12 and 18) in male rat SCN of 3, 12 and 24 months age groups. Age-induced decrease was observed in mean levels of NAS, MEL, 5-HIAA, 5-MIAA, 5-MTOH, and NAT and increase was observed in TRP, 5-HTP, 5-HT and 5-HTOH in rat SCN. Daily pulses decreased with aging significantly for TRP, 5-HT, NAS, MEL, 5-HIAA, 5-MIAA and NAT. We report here, the age-induced change in interactions between various 5-HT metabolism components by middle age (12 m) changing further by 24 m. The daily rhythms persisted with aging for NAS, MEL and 5-HTOH. Though, rhythms were abolished for TRP, 5-HTP, 5-HIAA, 5-MIAA, 5-MTOH and NAT differentially at 12 and 24 m. The MEL administration showed restoration in 5-HT ratio with 5-HTP, MEL and 5-HTOH in 24 m and NAS and 5-HIAA in 12 m SCN. Thus, MEL administration effects alterations of age-induced stoichiometry in levels and chronomics of serotonin metabolic network interactomes.

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Melatonin has differential effects on age-induced stoichiometric changes in daily chronomics of serotonin metabolism in SCN of male Wistar rats

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