Application of melatonin-mediated modulation of drought tolerance by regulating photosynthetic efficiency, chloroplast ultrastructure, and endogenous hormones in maize

Background Melatonin played an essential role in numerous vital life processes of animals and captured the interests of plant biologists because of its potent role in plants as well. As far as its possible contribution to photoperiodic processes, melatonin is believed to act as a growth regulator and a direct free radical scavenger/indirect antioxidant. The objective of this study to identify a precise melatonin concentration for a particular application method to improve plant growth requires identification and clarification. Methods This work establishes unique findings by optimizing melatonin concentration in alleviating the detrimental effects of drought stress in maize. Maize plants were subjected to drought stress (40–45% FC) after treatments of melatonin soil drenching at different concentrations (50, 100, and 150 µM) to consider the changes of growth attribute, chlorophyll contents, photosynthetic rate, relative water content (RWC), chloroplast ultrastructure, endogenous hormonal mechanism, and grain yield. Results Our results showed that the application of melatonin treatments remarkably improved the plant growth attributes, chlorophyll contents, photosynthetic rate, RWC, hormonal mechanism, and grain yield plant−1 under drought conditions at a variable rate. Conclusion Our current findings hereby confirmed the mitigating potential of melatonin application 100 µM for drought stress by maintaining plant growth, hormone content, and grain yield of maize. We conclude that the application of melatonin to maize is effective in reducing drought stress tolerance. Graphical Abstract

Effects of long-term oral administration of melatonin on tear production, intraocular pressure, and tear and serum melatonin concentrations in healthy dogs

OBJECTIVE To evaluate the effects of long-term (30-day) oral administration of melatonin on tear production, intraocular pressure (IOP), and concentration of melatonin in the tears and serum of healthy dogs. ANIMALS 20 healthy sexually intact adult male dogs. PROCEDURES 10 dogs were given melatonin (0.3 mg/kg, PO, q 24 h, administered in food at 9 am), and 10 dogs were given a placebo. Tear and serum melatonin concentrations, IOP, and tear production (determined with a Schirmer tear test) were recorded before (baseline) and 30 minutes, 3 hours, and 5 hours after administration of melatonin or the placebo on day 1 and 30 minutes after administration of melatonin or the placebo on days 8, 15, and 30. RESULTS Data collection time had significant effects on tear production, IOP, and tear melatonin concentration but not on serum melatonin concentration. Treatment (melatonin vs placebo) had a significant effect on tear melatonin concentration, but not on tear production, IOP, or serum melatonin concentration; however, tear melatonin concentration was significantly different between groups only 30 minutes after administration on day 1 and not at other times. CLINICAL RELEVANCE In healthy dogs, long-term administration of melatonin at a dosage of 0.3 mg/kg, PO, every 24 hours did not have any clinically important effects on tear production, IOP, or serum or tear melatonin concentrations.

“Endogenous Melatonin Concentration Along with the Expression of Mitochondrial Regulator Genes is Elevated by the Serum Shock Process in the U87-MG Cell Line”

According to the World Health Organization, glioblastoma, also known as the fourth grade in the development of astrocytoma, is a glial tumor limited to the central nervous system with a strong ability to invade the brain parenchyma. Melatonin can be generated outside of the pineal gland tissue, according to new research. Melatonin is produced by mitochondria independently but in concert with cell demands, and it plays an important function in cell cycle and metabolism regulation. As a result, we set out to investigate the association between cell metabolism and the serum shock-induced increase in endogenous melatonin, as well as the percentage of cell proliferation.Background: Melatonin can be produced in the mitochondria organelle of glioblastoma cells without the involvement of the pineal gland, according to new research. Regarding the physiological function of melatonin secreted by the pineal gland in the regulation of rhythmicity, the goal of this study was to see if the glioblastoma cell's melatonin production ability could be influenced using a typical serum shock technique established for cellular rhythm regulator.Material and methods: First, U87-MG glioblastoma cells were cultured in a DMEM medium containing 10% FBS and then cells were treated with a standard serum shock process (no FBS, 8h). The concentration of melatonin was measured using ELISA method in supernatant and cell extracts of Shock and control groups. The cell proliferation was measured by using BrdU staining and flow cytometry assessment. The gene expression levels of some mitochondria or circadian related genes including TFAM, BMAL1, PPARGC1A(PGC1-α), and DNM1L(DRP1) were measured, using qRT-PCR method.Results: In comparison to the control group, serum shock treated U87-MG glioblastoma cells had higher concentrations of cellular and released endogenous melatonin (two times). At the mRNA level, we discovered considerable upregulation of mitochondrial or circadian regulator genes (TFAM, BMAL1, PPARGC1A, and DNM1L); in the shock group compared to the control group (P <0.0002). Furthermore, although the percentage of proliferative cells (Brdu positive) was higher in the shock group, it was not statistically significant.Conclusion: The serum shock procedure has a significant impact on the U87-MG cell line's cellular activity. In terms of the study's findings, it's worth noting that an increase in endogenous melatonin concentration influences several signaling pathways within the U87-MG cell line, as seen by the increased expression of candidate genes.In light of the findings of this study, it's worth noting that further research into the role of endogenous melatonin and its effects on cancer cells is critical, and that comparing the results of normal and cancer cells can reveal the hotspots of the signaling pathways involved, which could facilitate in better understanding the biology of glioblastoma.

Melatonin and Epilepsy

Epilepsy is a chronic neurological disease with recurrent seizures. Its incidence, the social and psychological aspects of epilepsy-associated stigmatization in society, the medical risk of severe seizures, and the challenges in treatment confirm its medical and social significance. The pathogenesis of the diseases is associated with abnormal activity of a population of neurons due to various mechanisms, the most frequent being oxidative stress, glutamate excitotoxicity, and mitochondrial dysfunction. In the last 3-4 decades, the possible connection between epilepsy and melatonin &ndash; a neurohormone secreted by the pineal gland &ndash; has been sought and studied. Various physiological functions of melatonin in humans have been proven &ndash; regulation of circadian rhythms (diurnal, seasonal), sleep and wakefulness, participation in the processes of thermoregulation, tumour growth and aging, sexual activity and reproductive functions. It also has immunomodulatory, cytoprotective and antioxidant activity. The results from the studies with experimental models with animals conducted so far in search of a correlation between melatonin and epileptogenesis are mainly in support of the hypothesis of its anticonvulsant effect. The studies with humans are diverse in design, with a smaller number of participants, and the results are not always in explicit support of this hypothesis. The correlation between melatonin concentration and the course of the disease in patients with epilepsy has been discussed. The possibility of adding melatonin to anti-epileptic therapy has also been studied recently.

Peripheral Clock System Abnormalities in Patients With Parkinson’s Disease

Objective: To evaluate the altered expression of peripheral clock genes, circulating melatonin levels, and their correlations with sleep-wake phenotypes including probable rapid eye movement sleep behavior disorder (pRBD) symptoms in a relatively large population of Parkinson’s disease (PD) patients.Methods: We determined the expression profiles of five principal clock genes, BMAL1, CLOCK, CRY1, PER1, and PER2, in the peripheral blood mononuclear cells (PBMCs) of PD patients (n = 326), and healthy controls (HC, n = 314) using quantitative real-time PCR. Melatonin concentration in the plasma of two groups was evaluated by enzyme-linked immunosorbent assay. Then we performed comprehensive association analyses on the PBMCs clock gene expression, plasma melatonin levels and sleep characteristics.Results: Our data showed that the expression levels of BMAL1, CLOCK, CRY1, PER1, and PER2 were significantly decreased in the PBMCs of PD as compared with that of HC (P &lt; 0.05). PD patients had reduced plasma melatonin levels compared with HC (P &lt; 0.0001). pRBD and excessive daytime sleepiness are common in these PD patients and are associated with the expression levels of all five clock genes (r = −0.344∼−0.789, P &lt; 0.01) and melatonin concentration (r = −0.509∼−0.753, P &lt; 0.01). Statistical analyses also revealed that a combination of five clock genes and melatonin could reach a high diagnostic performance (areas under the curves, 97%) for PD comorbid pRBD.Conclusion: This case-control study demonstrates that peripheral BMAL1, CLOCK, CRY1, PER1, PER2, and melatonin levels are altered in PD patients and may serve as endogenous markers for sleep and wakefulness disturbances of PD.

Effects of Duodenal 5-Hydroxytryptophan Perfusion on Melatonin Synthesis in GI Tract of Sheep

The purpose of this study is to investigate the potential effects of 5-hydroxytryptophan (5-HTP) duodenal perfusion on melatonin (MT) synthesis in the gastrointestinal (GI) tract of sheep. 5-hydroxytryptophan is a precursor in the melatonin synthetic pathway. The results showed that this method significantly increased melatonin production in the mucosa of all segments in GI tract including duodenum, jejunum, ileum, cecum and colon. The highest melatonin level was identified in the colon and this indicates that the microbiota located in the colon may also participate in the melatonin production. In addition, portion of the melatonin generated by the GI tract can pass the liver metabolism and enters the circulation via portal vein. The current study provides further evidence to support that GI tract is the major site for melatonin synthesis and the GI melatonin also contributes to the circulatory melatonin level since plasma melatonin concentrations in 5-HTP treated groups were significantly higher than those in the control group. In conclusion, the results show that 10–50 mg of 5-HTP flowing into the duodenum within 6 h effectively improve the production of melatonin in the GI tract and melatonin concentration in sheep blood circulation during the day.

Supplementary Tryptophan Fed to Sows Prior to and after Farrowing to Improve Piglet Growth and Survival

Tryptophan indirectly increases plasma calcium levels, which may improve sow health, and melatonin production, which may improve piglet survival when supplemented during late gestation and lactation. It was hypothesised that tryptophan would increase piglet survival and increase sow circulating melatonin and calcium. Seventy-two multiparous (Landrace x Large White) sows were allocated to either control (0.16% tryptophan; n = 24), low tryptophan (0.42%; n = 24) or high tryptophan (0.56%; n = 24). Piglet viability measures consisted of weights, behaviour, meconium staining, rectal temperature, blood glucose and serum immunoglobulin G concentration. Blood samples collected from sows were analysed for melatonin (two daytime and three night-time samples; n = 17) and calcium (two samples pre- and post-farrowing; n = 14). Both tryptophan treatments increased piglet survival compared to the control group (p < 0.001). Tryptophan had no effect on piglet viability (p > 0.05) and no effect on sow plasma melatonin and calcium concentrations compared with the control group (p > 0.05) except at 21:00 when low tryptophan sows had higher melatonin concentration compared with high tryptophan (p = 0.011). Further research to understand the mediating effects of tryptophan (particularly 5-hydroxytryptophan) on piglet survival, including sow behaviour, is warranted.

Abnormal night melatonin level in a patient with well-controlled epilepsy without sleep disturbances – could it be associated with levetiracetam therapy: A case report

We present a case report of a 23-year old male with newly diagnosed epilepsy manifested with generalized tonic seizures. Levetiracetam (LEV) was started and the patient was seizure free. The patient demonstrated intermediate chronotype determined by the Morningness-Eveningness Questionnaire (MEQ). There was no epileptiform activity on electroencephalography (EEG) and polysomnography (PSG), sleep architecture disturbances (PSG) or daytime sleepiness (Epworth sleepiness score, Multiple sleep latency test) at the onset and after 3 months of LEV therapy. The melatonin serum levels after 3 months of LEV treatment were 22.00 pg/ml at 3 a.m. and 23.60 pg/ml at 8 a.m. - there was no normal night peak concentration. This abnormality may be associated with a later night peak melatonin concentration, the treatment with levetiracetam being a possible explanation. We consider the presented clinical case of special interest because of the combination of absence of normal night peak melatonin concentration, normal sleep parameters and non-extremely presented chronotype. We suggest that such patients could benefit from add-on therapy with melatonin.