Endogenous Melatonin Levels Research Articles

Exogenous melatonin delays postharvest fruit senescence and maintains the quality of sweet cherries

We assessed the effects of postharvest exogenous melatonin (50,100 and 150 µmol L−1) on the senescence and quality of sweet cherries during storage at 0 ± 0.5 °C. Melatonin treatment decreased decay incidence, respiration rate, and weight loss. It delayed the degradation of firmness, lightness, saturation, hue angle, titratable acidity, and total soluble solids content, thus maintaining better fruit quality. Melatonin treatment inhibited increases in O2−, H2O2, malondialdehyde content, and relative membrane permeability, while maintaining higher endogenous melatonin levels and increasing superoxide dismutase and catalase activity. Additionally, melatonin treatment enhanced the activity of antioxidant enzymes, increased the levels of ascorbic acid, and reduced glutathione levels, which are related to the ascorbate–glutathione cycle, as well as increasing the AsA:DHA and GSH:GSSG ratios. Delayed senescence in sweet cherries after exogenous melatonin treatment may be associated with high endogenous melatonin levels and increased antioxidant activity and content.

Relationship between endogenous melatonin concentrations and uterine contractions in late third trimester of human pregnancy.

In humans, circulating levels of the hormone melatonin and the initiation of spontaneous labor are both higher at night than during the day. Since activation of uterine melatonin receptors can stimulate human in vitro uterine contractions and these receptors are only expressed on the uterine tissue of women in labor, we hypothesized that circulating melatonin concentrations would affect uterine contractions in vivo. We evaluated the impact of light-induced modulation of melatonin secretion on uterine contractions in women during late third trimester (~36-39weeks) of pregnancy in two inpatient protocols. We found a significant (P<0.05) positive linear association between circulating melatonin concentrations and the number of uterine contractions under both protocols. On average, uterine contractions increased between 1.4 and 2.1 contractions per 30minutes for every 10pg/mL*h increase in melatonin concentration. These findings have both basic science and clinical implications for pregnant women, since endogenous melatonin levels and melatonin receptor activity can be altered by light and/or pharmaceutical agents.

Melatonin: A Small Molecule but Important for Salt Stress Tolerance in Plants.

Salt stress is one of the most serious limiting factors in worldwide agricultural production, resulting in huge annual yield loss. Since 1995, melatonin (N-acetyl-5-methoxytryptamine)—an ancient multi-functional molecule in eukaryotes and prokaryotes—has been extensively validated as a regulator of plant growth and development, as well as various stress responses, especially its crucial role in plant salt tolerance. Salt stress and exogenous melatonin lead to an increase in endogenous melatonin levels, partly via the phyto-melatonin receptor CAND2/PMTR1. Melatonin plays important roles, as a free radical scavenger and antioxidant, in the improvement of antioxidant systems under salt stress. These functions improve photosynthesis, ion homeostasis, and activate a series of downstream signals, such as hormones, nitric oxide (NO) and polyamine metabolism. Melatonin also regulates gene expression responses to salt stress. In this study, we review recent literature and summarize the regulatory roles and signaling networks involving melatonin in response to salt stress in plants. We also discuss genes and gene families involved in the melatonin-mediated salt stress tolerance.

Melatonin Improved Waterlogging Tolerance in Alfalfa (Medicago sativa) by Reprogramming Polyamine and Ethylene Metabolism.

Melatonin (MT), polyamines (PAs), and ethylene have been suggested to play key roles in plant growth and development in response to environmental abiotic stresses. However, the effect of melatonin on polyamine and ethylene metabolism under waterlogging stress has rarely been elucidated. The main purpose of this study was to investigate the effect of melatonin pretreatment on waterlogging stress in alfalfa. The experiment was arranged into four treatment groups control with water pretreatment (CK-MT), control with melatonin pretreatment (CK+MT), waterlogging pretreated with water (WL-MT) and waterlogging pretreated with melatonin (WL+MT), with three replications. Six-week-old alfalfa seedlings were pretreated with 100 μM melatonin and exposed to waterlogging stress for 10 days. Plant growth rate, different physiological characteristics, and gene expression level were measured. Results showed that waterlogging induced melatonin accumulation, and melatonin pretreatment increased endogenous MT levels for the control and water-logged plants. Waterlogging stress caused a significant reduction in plant growth, chlorophyll content, photochemical efficiency (Fv/Fm) and net photosynthetic rate (Pn), while also causing increased leaf electrolyte leakage (EL) and malondialdehyde (MDA) content. Pretreatment with melatonin alleviated the waterlogging-induced damage and reduction in plant growth, chlorophyll content, Fv/Fm and Pn. Waterlogging stress significantly increased leaf polyamines (Put, Spd, Spm) and ethylene levels, and the increased PAs and ethylene levels are coupled with higher metabolic enzymes and gene expressions. While pretreatment with melatonin further increased Put, Spd and Spm levels, it also decreased ethylene levels under waterlogging, and those increased PAs levels or decreased ethylene levels are regulated by the metabolic enzymes and gene expressions. The results in this study provide more comprehensive insight into the physiological and molecular mechanisms of melatonin-improved waterlogging tolerance in alfalfa. Furthermore, they suggested that melatonin improved waterlogging tolerance in alfalfa at least partially by reprogramming ethylene and PA biosynthesis, attributable to the increased PAs and decreased ethylene levels, which leads to more enhanced membrane stability and photosynthesis as well as less leaf senescence caused by ethylene.

Antioxidative response of Melissa officinalis L. and Valeriana officinalis L. leaves exposed to exogenous melatonin and excessive zinc and cadmium level

Heavy metals disturb the redox homeostasis of the plant cell. The indolamine hormone, melatonin, protects plants from oxidative damage by directly scavenging reactive oxygen species or by stimulating the activity of antioxidant enzymes. The antioxidative role of melatonin in the leaves of two medicinal plants, lemon balm (Melissa officinalis L.) and valerian (Valeriana officinalis L.) that were treated with increased concentrations of Zn and Cd 24 h after sowing at an open field, were investigated. The plants were treated with Zn, Cd, melatonin and a mixture of melatonin with the mentioned metals. Exogenously added melatonin increased the endogenous melatonin concentration in lemon balm leaves. However, in the valerian leaves, lower or the same endogenous melatonin level was detected. The significantly higher concentration of endogenous melatonin in both plants was measured after treatment with Zn. As the results showed, changes in superoxide dismutase (SOD) and peroxidase (POD) activities are species-specific and change depending on the plant development phase, and the type of treatment. Melatonin pretreatment induced alternation in SOD isoenzyme profiles and activities as well as POD activity in both plant species treated with heavy metals.

Abnormal Hippocampal Melatoninergic System: A Potential Link between Absence Epilepsy and Depression-Like Behavior in WAG/Rij Rats?

Absence epilepsy and depression are comorbid disorders, but the molecular link between the two disorders is unknown. Here, we examined the role of the melatoninergic system in the pathophysiology of spike and wave discharges (SWDs) and depression-like behaviour in the Wistar Albino Glaxo from Rijswijk (WAG/Rij) rat model of absence epilepsy. In WAG/Rij rats, SWD incidence was higher during the dark period of the light-dark cycle, in agreement with previous findings. However, neither pinealectomy nor melatonin administration had any effect on SWD incidence, suggesting that the melatoninergic system was not involved in the pathophysiology of absence-like seizures. Endogenous melatonin levels were lower in the hippocampus of WAG/Rij rats as compared to non-epileptic control rats, and this was associated with higher levels of melatonin receptors in the hippocampus, but not in the thalamus. In line with the reduced melatonin levels, cell density was lower in the hippocampus of WAG/Rij rats and was further reduced by pinealectomy. As expected, WAG/Rij rats showed an increased depression-like behaviour in the sucrose preference and forced swim tests, as compared to non-epileptic controls. Pinealectomy abolished the difference between the two strains of rats by enhancing depression-like behaviour in non-epileptic controls. Melatonin replacement displayed a significant antidepressant-like effect in both WAG/Rij and control rats. These findings suggest that a defect of hippocampal melatoninergic system may be one of the mechanisms underlying the depression-like phenotype in WAG/Rij rats and that activation of melatonin receptors might represent a valuable strategy in the treatment of depression associated with absence epilepsy.

Endogenous melatonin deficiency aggravates high temperature-induced oxidative stress in Solanum lycopersicum L.

Melatonin is a natural biostimulating molecule that occurs in a number of plant species. Despite a short history of phytomelatonin research, the critical roles of melatonin in plant stress responses have extensively been documented. However, the majority of such studies constitute ‘pharmacological approach’ and studies exploring the relevance of endogenous melatonin are scanty. As an attempt to unmask the role of endogenous melatonin in plant thermotolerance, we generated melatonin deficient tomato plants by silencing a gene, CAFFEIC ACID O-METHYLTRANSFERASE 1 (COMT1), involved in melatonin biosynthesis. We first examined the effect of exogenous melatonin and then performed a detailed analysis of the effect of melatonin deficiency on oxidative stress markers, enzymatic and non-enzymatic antioxidants, and redox homeostasis in tomato plants. The results showed that suppression of endogenous melatonin had an opposite effect of exogenous melatonin on tomato tolerance to high temperature stress. Endogenous melatonin deficiency aggravated high temperature-induced oxidative stress as evidenced by increased electrolyte leakage percentage, malondialdehyde concentration, and oxidized and insoluble protein accumulation in tomato leaves. These changes were accompanied with the significant reductions in the activity of ascorbate peroxidase and catalase, two key antioxidant enzymes that play prominent role in plant thermotolerance. Furthermore, silencing of COMT1 altered redox balance as reflected by the significantly decreased ratios of GSH:GSSG and AsA:DHA under high temperature stress. In contrast, exogenous melatonin augmented the endogenous melatonin level in COMT1-silenced plants and alleviated the heat-induced oxidative stress. Our results suggest that an optimal endogenous melatonin level is critical, not only for its self-antioxidant capacity, but also for maintaining an efficient enzymatic antioxidant system and redox homeostasis under perturbed environmental conditions.

Changes in Melatonin, Cortisol, and Body Temperature, and the Relationship Between Endogenous Melatonin Levels and Analgesia Consumption in Patients Undergoing Bariatric Surgery.

Melatonin has analgesic, anti-inflammatory, sedative, and anxiolytic properties. However, the relationship between endogenous melatonin levels and postoperative analgesic requirements has not been well elucidated in patients undergoing bariatric surgery. We studied endogenous melatonin levels, cortisol levels, body temperatures, and the relationship between the level of endogenous melatonin and postoperative morphine consumption. The trial was conducted among 30 patients who were scheduled for laparoscopic bariatric surgery. Their ages were between 18 and 65years and their BMIs were above 40kg/m2. Secretion of melatonin, cortisol, and body temperature was monitored before the anesthetic induction, at 2h intraoperatively, and at 2, 6, 10, (2:00 A.M.) and 24h postoperatively. For each patient, morphine consumption was assessed at postoperative visits. The primary outcomes were to measure endogenous melatonin levels and to examine the relationship between these levels and morphine consumption. The secondary outcome was to observe the changes in cortisol and body temperature. There was a significant decrease in melatonin levels when preoperative melatonin levels were compared with intraoperative and all postoperative follow-up periods (p< 0.05). When the correlation between plasma melatonin levels and the postoperative morphine consumption of the patients was inspected, there was a significant correlation in all of the follow-up periods (p< 0.05). When preoperative cortisol levels were compared with intraoperative and postoperative cortisol levels, there was a significant difference in the follow-up periods, except two periods (p< 0.05). Body temperatures were similar in all measurement periods. Endogenous melatonin secretion was significantly decreased in the intraoperative and postoperative periods. Furthermore, there was a significant inverse correlation between changes in endogenous melatonin levels and morphine consumption. Clinical Trial Number NCT03107702 from A service of the U.S. National Institutes of Health, clinicaltrials.gov.

Melatonin biosynthesis enzymes recruit WRKY transcription factors to regulate melatonin accumulation and transcriptional activity on W-box in cassava.

Melatonin is widely involved in growth, development, and stress responses in plants. Although the melatonin synthesis enzymes have been identified in various plants, their interacting proteins remain unknown. Herein, overexpression of tryptophan decarboxylase 2 (MeTDC2)-interacting proteins, N-acetylserotonin O-methyltransferase 2 (MeASMT2) interacting proteins, and N-acetylserotonin O-methyltransferase 3 (MeASMT3) in cassava leaf protoplasts resulted in more melatonin than when other enzymes were overexpressed. Through yeast two-hybrid, 14 MeTDC2-interacting proteins, 24 MeASMT2 interacting proteins, and 9 MeASMT3-interacting proteins were identified. Notably, we highlighted MeWRKY20 and MeWRKY75 as common interacting proteins of the 3 enzymes, as evidenced by yeast two-hybrid, and in vivo bimolecular fluorescence complementation (BiFC). Moreover, co-overexpression of MeTDC2/MeASMT2/3 with MeWRKY20/75 in cassava leaf protoplasts did not only activated the transcriptional activities of MeWRKY20 and MeWRKY75 on W-box, but also induced the effects of MeTDC2, MeASMT2/3 on endogenous melatonin levels. Taken together, 3 melatonin synthesis enzymes (MeTDC2, MeASMT2/3) interact with MeWRKY20/75 to form a protein complex in cassava. This information significantly extends the knowledge of the complex modulation of plant melatonin signaling.

Exogenous Melatonin Confers Cadmium Tolerance by Counterbalancing the Hydrogen Peroxide Homeostasis in Wheat Seedlings.

Melatonin has emerged as a research highlight regarding its important role in regulating plant growth and the adaptation to the environmental stresses. In this study, we investigated how melatonin prevented the cadmium toxicity to wheat seedlings. The results demonstrated that cadmium induced the expression of melatonin biosynthesis-related genes and cause a significant increase of endogenous melatonin level. Melatonin treatment drastically alleviated the cadmium toxicity, resulting in increased plant height, biomass accumulation, and root growth. Cadmium and senescence treatment significantly increased the endogenous level of hydrogen peroxide, which was strictly counterbalanced by melatonin. Furthermore, melatonin treatment caused a significant increase of GSH (reduced glutathione) content and the GSH/GSSG (oxidized glutathione) ratio. The activities of two key antioxidant enzymes, ascorbate peroxidase (APX) and superoxide dismutase (SOD), but not catalase (CAT) and peroxidase (POD), were specifically improved by melatonin. Additionally, melatonin not only promoted the primary root growth, but also drastically enhanced the capacity of the seedling roots to degrade the exogenous hydrogen peroxide. These results suggested that melatonin played a key role in maintaining the hydrogen peroxide homeostasis, via regulation of the antioxidant systems. Conclusively, this study revealed a crucial protective role of melatonin in the regulation of cadmium resistance in wheat.

Crosstalk between calcium and melatonin affects postharvest physiological deterioration and quality loss in cassava

Rapid postharvest physiological deterioration largely reduces the quality and marketability of cassava. The molecular mechanism underlying cassava postharvest physiological deterioration and quality loss is largely unknown. The present study aimed to investigate the role of calcium and its relationship with melatonin in cassava postharvest physiological deterioration. Transcriptomic analyses indicate that most of the calcium ion (Ca2+) sensor genes are upregulated in cassava tuberous roots at different postharvest stages. Exogenous CaCl2 reduces postharvest physiological deterioration, increases the endogenous levels of Ca2+ and melatonin, reduces the degradation of ascorbic acid and starch, and induces the expression of genes related to melatonin biosynthesis after harvest. These effects are reversed by the exogenous application of a Ca2+ chelator (EGTA). Exogenous melatonin also increases endogenous melatonin levels and reduces ascorbic acid and starch degradation during postharvest physiological deterioration but do not affect endogenous Ca2+ content. Together, these findings demonstrate that calcium-induced activation of melatonin biosynthesis plays a role in reducing postharvest physiological deterioration and quality loss in cassava. Additionally, pretreatment with EGTA arrests the melatonin-induced reduction of postharvest physiological deterioration, suggesting the possible crosstalk between melatonin and calcium during postharvest physiological deterioration.

Food-induced reinforcement is abrogated by the genetic deletion of the MT1 or MT2 melatonin receptor in C3H/HeN mice

Palatable food is known for its ability to enhance reinforcing responses. Studies have suggested a circadian variation in both drug and natural reinforcement, with each following its own time course. The goal of this study was to determine the role of the MT1 and MT2 melatonin receptors in palatable snack food-induced reinforcement, as measured by the conditioned place preference (CPP) paradigm during the light and dark phases. C3H/HeN wild-type mice were trained for snack food-induced CPP at either ZT 6 – 8 (ZT: Zeitgeber time; ZT 0 = lights on), when endogenous melatonin levels are low, or ZT 19 – 21, when melatonin levels are high. These time points also correspond to the high and low points for expression of the circadian gene Period1, respectively. The amount of snack food (chow, Cheetos®, Froot Loops® and Oreos®) consumed was of similar magnitude at both times, however only C3H/HeN mice conditioned to snack food at ZT 6 – 8 developed a place preference. C3H/HeN mice with a genetic deletion of either the MT1 (MT1KO) or MT2 (MT2KO) receptor tested at ZT 6 – 8 did not develop a place preference for snack food. Although the MT2KO mice showed a similar amount of snack food consumed when compared to wild-type mice, the MT1KO mice consumed significantly less than either genotype. We conclude that in our mouse model snack food-induced CPP is dependent on time of day and the presence of the MT1 or MT2 receptors, suggesting a role for melatonin and its receptors in snack food-induced reinforcement.

RAV transcription factors are essential for disease resistance against cassava bacterial blight via activation of melatonin biosynthesis genes.

With 1 AP2 domain and 1 B3 domain, 7 MeRAVs in apetala2/ethylene response factor (AP2/ERF) gene family have been identified in cassava. However, the in vivo roles of these remain unknown. Gene expression assays showed that the transcripts of MeRAVs were commonly regulated after Xanthomonas axonopodis pv manihotis (Xam) and MeRAVs were specifically located in plant cell nuclei. Through virus-induced gene silencing (VIGS) in cassava, we found that MeRAV1 and MeRAV2 are essential for plant disease resistance against cassava bacterial blight, as shown by the bacterial propagation of Xam in plant leaves. Through VIGS in cassava leaves and overexpression in cassava leave protoplasts, we found that MeRAV1 and MeRAV2 positively regulated melatonin biosynthesis genes and the endogenous melatonin level. Further investigation showed that MeRAV1 and MeRAV2 are direct transcriptional activators of 3 melatonin biosynthesis genes in cassava, as evidenced by chromatin immunoprecipitation-PCR in cassava leaf protoplasts and electrophoretic mobility shift assay. Moreover, cassava melatonin biosynthesis genes also positively regulated plant disease resistance. Taken together, this study identified MeRAV1 and MeRAV2 as common and upstream transcription factors of melatonin synthesis genes in cassava and revealed a model of MeRAV1 and MeRAV2-melatonin biosynthesis genes-melatonin level in plant disease resistance against cassava bacterial blight.

Ameliorative effects of melatonin on dark-induced leaf senescence in gardenia (Gardenia jasminoides Ellis): leaf morphology, anatomy, physiology and transcriptome

Cut gardenia (Gardenia jasminoides Ellis) foliage is widely used as a vase material or flower bouquet indoors; however, insufficient indoor light accelerates its senescence, which shortens its viewing time. In this study, applying melatonin to delay gardenia leaf senescence when exposed to extremely low light condition (darkness), and the results showed that 1.0 mM was the effective concentration. At this concentration, chlorophyll contents and chlorophyll fluorescence parameters (Fv/Fm, Fv/F0 and Y(II)) increased, while the carotenoid and flavonoid contents decreased. Meanwhile, stress physiological indices decreased in response to exogenous melatonin application, whereas an increase in glutamine synthetase activity, water and soluble protein contents was observed. Moreover, exogenous melatonin application also reduced leaf programmed cell death under darkness, increased the endogenous melatonin level, expression levels of tryptophan decarboxylase gene, superoxide dismutase and catalase activities and the ascorbate–glutathione cycle, and maintained more intact anatomical structures. Furthermore, transcriptome sequencing revealed that various biological processes responded to exogenous melatonin application, including carbohydrate metabolism, amino acid metabolism, lipid metabolism, plant hormone signal transduction and pigment biosynthesis. Consequently, dark-induced leaf senescence in gardenia was significantly delayed. These results provided a better understanding for improving the ornamental value of cut gardenia foliage using melatonin.

Deciphering the Function of the Blunt Circadian Rhythm of Melatonin in the Newborn Lamb: Impact on Adrenal and Heart.

Neonatal lambs, as with human and other neonates, have low arrhythmic endogenous levels of melatonin for several weeks until they start their own pineal rhythm of melatonin production at approximately 2 weeks of life. During pregnancy, daily rhythmic transfer of maternal melatonin to the fetus has important physiological roles in sheep, nonhuman primates, and rats. This melatonin rhythm provides a circadian signal and also participates in adjusting the physiology of several organs in preparation for extrauterine life. We propose that the ensuing absence of a melatonin rhythm plays a role in neonatal adaptation. To test this hypothesis, we studied the effects of imposing a high-amplitude melatonin rhythm in the newborn lamb on (1) clock time-related changes in cortisol and plasma variables and (2) clock time-related changes of gene expression of clock genes and selected functional genes in the adrenal gland and heart. We treated newborn lambs with a daily oral dose of melatonin (0.25 mg/kg) from birth to 5 days of age, recreating a high-amplitude melatonin rhythm. This treatment suppressed clock time-related changes of plasma adrenocorticotropic hormone, cortisol, clock gene expression, and functional genes in the newborn adrenal gland. In the heart, it decreased heart/body weight ratio, increased expression of Anp and Bnp, and resulted in different heart gene expression from control newborns. The interference of this postnatal melatonin treatment with the normal postnatal pattern of adrenocortical function and heart development support a physiological role for the window of flat postnatal melatonin levels during the neonatal transition.

Melatonin Secretion Is Increased in Children with Severe Traumatic Brain Injury.

Background: Traumatic brain injury (TBI) is a leading cause of death and disability in children. Oxidative stress plays a significant role in brain damage and melatonin exhibits both direct and indirect antioxidant effects. The primary aim of the present study was to evaluate serum melatonin levels in children with severe TBI in comparison to critically ill children admitted to the Pediatric Intensive Care Unit for conditions other than TBI. Methods: Twenty-four children were evaluated, equally divided into severe TBI and no-TBI. Blood samples for serum melatonin analysis were collected at 22:00, 01:00, 03:00, 05:00, 08:00, and 12:00. Results: Mean serum melatonin peaks in children of the TBI group were higher compared to the values of no-TBI critically ill children (495 ± 102 vs. 294 ± 119 pg/mL, p = 0.0002). Furthermore, the difference was even more significant in comparison to values reported in literature for healthy age-matched children (495 ± 102 vs. 197 ± 71 pg/mL, p < 0.0001). Conclusion: This study has shown that endogenous serum melatonin levels dramatically increase in children after severe TBI. This elevation is likely to represent a response to oxidative stress and/or inflammation due to severe head injury.

Melatonin: Possibilities for use in the treatment of asthma

Asthma is a serious health problem affecting all age groups. Melatonin or its agonists are commonly used to treat many diseases, but there are conflicting data on asthma therapy. This paper analyzes researches on the possible use of melatonin in the therapy of asthma. Melatonin is a potent antioxidant and a vasodilator, but in some experiments, it can act as a pro-oxidant and a vasoconstrictor, which may depend on the duration of use. It has been suggested that circadian rhythms should be corrected in asthmatics to optimize the desired effects of drugs and to reduce the severity of their adverse reactions. Disordered diurnal variations in the salivary levels of melatonin and cortisol are detectable in patients with asthma and may be implicated in its pathogenesis. In addition, the conflicting data on the effect of melatonin on the development of asthma are associated with an incomplete view of the factors influencing the level of melatonin. Thus, to study the effects of melatonin, it is necessary to take into account the greatest possible factors that may influence the level of melatonin and the course of asthma: a daily diet in terms of the use of caffeine, alcohol, sleep-wakefulness pattern, sleep quality proper, and drowsiness during the daytime, social burden, the level of anxiety and stress resistance, and to investigate the levels of endogenous melatonin or its derivatives, immune status, oxidative stress intensity, etc. Obviously, the use of melatonin in the therapy of asthma can be considered, by applying a personalized approach.

Endophytic Bacterium Pseudomonas fluorescens RG11 May Transform Tryptophan to Melatonin and Promote Endogenous Melatonin Levels in the Roots of Four Grape Cultivars.

Endophytes have been verified to synthesize melatonin in vitro and promote abiotic stress-induced production of endogenous melatonin in grape (Vitis vinifera L.) roots. This study aimed to further characterize the biotransformation of tryptophan to melatonin in the endophytic bacterium Pseudomonas fluorescens RG11 and to investigate its capacity for enhancing endogenous melatonin levels in the roots of different grape cultivars. Using ultra performance liquid chromatography-tandem mass spectrometry combined with 15N double-labeled L-tryptophan as the precursor for melatonin, we detected isotope-labeled 5-hydroxytryptophan, serotonin, N-acetylserotonin, and melatonin, but tryptamine was not detected during the in vitro incubation of P. fluorescens RG11. Furthermore, the production capacity of these four compounds peaked during the exponential growth phase. RG11 colonization increased the endogenous levels of 5-hydroxytryptophan, N-acetylserotonin, and melatonin, but reduced those of tryptamine and serotonin, in the roots of the Red Globe grape cultivar under salt stress conditions. Quantitative real-time PCR revealed that RG11 reduced the transcription of grapevine tryptophan decarboxylase and serotonin N-acetyltransferase genes when compared to the un-inoculated control. These results correlated with decreased reactive oxygen species bursts and cell damage, which were alleviated by RG11 colonization under salt stress conditions. Additionally, RG11 promoted plant growth and enhanced the levels of endogenous melatonin in different grape cultivars. Intraspecific variation in the levels of melatonin precursors was found among four grape cultivars, and the associated root crude extracts appeared to significantly induce RG11 melatonin biosynthesis in vitro. Overall, this study provides useful information that enhances the existing knowledge of a potential melatonin synthesis pathway in rhizobacteria, and it reveals plant–rhizobacterium interactions that affect melatonin biosynthesis in plants subjected to abiotic stress conditions.

Improved cold tolerance in Elymus nutans by exogenous application of melatonin may involve ABA-dependent and ABA-independent pathways

Melatonin is an important secondary messenger that plays a central role in plant growth, as well as abiotic and biotic stress tolerance. However, the underlying physiological and molecular mechanisms of melatonin-mediated cold tolerance, especially interactions between melatonin and other key molecules in the plant stress response, remain unknown. Here, the interrelation between melatonin and abscisic acid (ABA) was investigated in two genotypes of Elymus nutans Griseb., the cold-tolerant Damxung (DX) and the cold-sensitive Gannan (GN) under cold stress. Pre-treatment with exogenous melatonin or ABA alleviated oxidative injury via scavenging ROS, while enhancing both antioxidant enzyme activities and non-enzymatic antioxidant contents. Treatment of fluridone, an ABA biosynthesis inhibitor caused membrane lipid peroxidation and lowered melatonin-induced antioxidant defense responses. It is worth noting that cold stress significantly induced both endogenous melatonin and ABA levels in both genotypes. Application of melatonin increased ABA production, while fluridone significantly suppressed melatonin-induced ABA accumulation. ABA and fluridone pre-treatments failed to affect the endogenous melatonin concentration. Moreover, exogenous melatonin up-regulated the expression of cold-responsive genes in an ABA-independent manner. These results indicate that both ABA-dependent and ABA-independent pathways may contribute to melatonin-induced cold tolerance in E. nutans.

Melatonin in pediatric neurology

Melatonin is a hormone produced by the pineal gland during the night, as a response to the light-darkness variation. The endogenous melatonin levels have a cyclic evolution throughout the entire life. Various roles have been cited such as the in utero developement of the fetus through its action on the placenta, neurons and glial cells, a major role in the regulation of the cyrcadian rhythm, antioxidative, antiinflammatory roles, as well as celullar and umoral immunity modulation. In the European Union, exogenous melatonin has been evaluated by the European Food Safety Authority (EFSA) for reducing sleep onset latency and the conclusion was that it has efficacy studies in this regard.