Plasma Melatonin Levels Research Articles

Effects of different light-emitting diode light on hatch performance, embryo development, eye structure, and plasma melatonin in layer incubation

Light intensity, wavelength, and photoperiod have a combined effect on chicken incubation. This study was conducted to evaluate the effect of 12-h light, 12-h dark (12L:12D) photoperiod of white light (380-780 nm, WL), blue light (455/447.5-462.5 nm, BL), and green light (525/515-535 nm, GL) in chicken perceived light intensity during layer incubation on hatching performance, embryo development, eye structure, and melatonin concentration. Three batches of eggs from Jinghong No. 1 layer breeder were used in this experiment. Light stimulation had no effect on hatchability, and no consistent effect on embryo weight and newly hatched chick weight. However, the average hatching time of white light group and green light group was 7.3 h and 5.5 h later than that of the control group. Therefore, the holding period of chicks was significantly shortened (P=0.001) in these 2 light groups. Light stimulation had a significant effect on the thickness of retinal layers (P < 0.05), retinal layers of white light group was thicker than that of the other 3 groups. Melatonin levels of chicks hatched in the green light and blue light were significantly higher than that of chicks hatched in the white light and darkness (P < 0.05). It indicated that the monochrome green and blue light promoted the expression of melatonin in chicken embryos. No significant diurnal rhythms were found at the level of plasma melatonin in 4 groups on d 21 using cosine analysis. It was concluded that green light has a positive effect on embryo development and melatonin secretion, while white light probably has positive effect on eye development. Furthermore, both green and white light stimulation resulted in late hatch for layer egg incubation. The obtained results are important in determining the light protocol for chicken incubation.

Nocturnal melatonin increases glucose uptake via insulin-independent action in the goldfish brain.

Melatonin, a neurohormone nocturnally produced by the pineal gland, is known to regulate the circadian rhythm. It has been recently reported that variants of melatonin receptors are associated with an increased risk of hyperglycemia and type 2 diabetes, suggesting that melatonin may be involved in the regulation of glucose homeostasis. Insulin is a key hormone that regulates circulating glucose levels and cellular metabolism after food intake in many tissues, including the brain. Although cells actively uptake glucose even during sleep and without food, little is known regarding the physiological effects of nocturnal melatonin on glucose homeostasis. Therefore, we presume the involvement of melatonin in the diurnal rhythm of glucose metabolism, independent of insulin action after food intake. In the present study, goldfish (Carassius auratus) was used as an animal model, since this species has no insulin-dependent glucose transporter type 4 (GLUT4). We found that in fasted individuals, plasma melatonin levels were significantly higher and insulin levels were significantly lower during the night. Furthermore, glucose uptake in the brain, liver, and muscle tissues also significantly increased at night. After intraperitoneal administration of melatonin, glucose uptake by the brain and liver showed significantly greater increases than in the control group. The administration of melatonin also significantly decreased plasma glucose levels in hyperglycemic goldfish, but failed to alter insulin mRNA expression in Brockmann body and plasma insulin levels. Using an insulin-free medium, we demonstrated that melatonin treatment increased glucose uptake in a dose-dependent manner in primary cell cultures of goldfish brain and liver cells. Moreover, the addition of a melatonin receptor antagonist decreased glucose uptake in hepatocytes, but not in brain cells. Next, treatment with N1-acetyl-5-methoxykynuramine (AMK), a melatonin metabolite in the brain, directly increased glucose uptake in cultured brain cells. Taken together, these findings suggest that melatonin is a possible circadian regulator of glucose homeostasis, whereas insulin acquires its effect on glucose metabolism following food intake.

Repeated donkey milk consumption reduces anxiety-like behaviors and brain oxidative damage to lipids in mice

Donkey milk (DM) is a source of bioactive compounds that can benefit neural functioning. In the present study, we investigated the effects of DM consumption on anxiolytic-related, despair-like, locomotion and coordination behaviors, as well as the provision of protection from oxidative damage to lipids and proteins in brain tissues and melatonin plasma levels. To achieve this, male mice orally received DM (4 g.kg-1) or vehicle for 18 days. Their behavior was assessed in the following tests: elevated plus maze (EPM), open field and rotarod tests (OF, RR) and forced swimming test (FST). Acute treatments with diazepam (DZP, 1.5 mg.kg-1, v.o.), fluoxetine (FLX, 20 mg.kg-1, i.p.) and nortriptyline (NTP, 20 mg.kg-1, i.p.) were used as positive controls. On the eighteenth day, the animals were euthanized and brain tissue and blood were collected to measure oxidative damage, and melatonin plasma levels. Similar to DZP, repeated DM consumption reduced exploration to open areas in the EPM test. Under our experimental conditions, conventional antidepressants reduced immobility time in the FST, and the benzodiazepine treatment impaired motor coordination in mice. No significant differences in locomotion, motor coordination and despair-related behaviors were observed in the mice treated with DM when assessed in the EPM, OF, RR and FST, respectively. Biochemical assays showed that repeated DM exposition protected against oxidative damage to lipids and increased plasma levels of melatonin. These findings suggest consumption of DM may be a promising food for the treatment of anxiety-related disorders, without depressant effects on the central nervous system.

Novel approaches on melatonin role: Presence of clock-hormone in fish seminal plasma

The study of melatonin is of great importance for the fundamental knowledge of any living system since it displays many different physiological roles, including being a potent natural antioxidant. To the best of our knowledge, there is no information regarding melatonin in fish seminal plasma. This study aimed to determine this clock-hormone levels in the seminal plasma of three aquaculture fish species: European seabass (Dicentrarchus labrax), gilthead seabream (Sparus aurata), and Senegalese sole (Solea senegalensis) (both wild and F1 breeders), and to explore melatonin potential role in fish reproduction and spermatozoa antioxidant status. Blood and seminal plasma were collected from fish during their reproductive season, at two different times of the day [mid-light (ML) and mid-dark (MD)], and melatonin concentration was determined by radioimmunoassay (RIA). Testosterone (T), 11-ketotestosterone (11KT), and total antioxidant status (TAS) were also determined, to investigate the putative role of seminal melatonin in fish reproduction, both at endocrine and antioxidant levels. For each species, Pearson's correlation analysis was performed between all possible factors. Blood plasma melatonin showed higher average values at night in the three species: gilthead seabream (808 ± 139 pg/mL), European seabass (364 ± 85 pg/mL), and Senegalese sole (248 ± 40 and 88 ± 11 pg/mL in F1 and wild males, respectively). However, melatonin levels in seminal plasma were species-specific: in European seabass, melatonin levels were not detectable at any time-point, whereas in gilthead seabream it was only found at MD (average of 21 pg/mL), and in Senegalese sole, different melatonin patterns were observed between F1 and wild males, but both had higher melatonin at MD (6.84 and 14.26 pg/mL, respectively). In gilthead seabream, at MD seminal melatonin levels correlated with the antioxidant status of seminal plasma. A relationship between blood melatonin and seminal TAS levels was observed in European seabass at ML: in this species, seminal melatonin could not be detected and the lowest seminal TAS levels were found. Regarding steroid analysis, opposite patterns in the seminal plasma of F1 and wild Senegalese sole were observed: at MD, wild Senegalese sole had substantially greater 11KT levels (2.53 ng/mL), whereas F1 males had higher T levels (1.92 ng/mL). In gilthead seabream, a positive correlation between T and ML blood melatonin and seminal TAS was observed. This study unraveled the species-specificity and daily changes of melatonin in fish seminal plasma.

Synthetic torpor triggers a regulated mechanism in the rat brain, favoring the reversibility of Tau protein hyperphosphorylation.

Introduction: Hyperphosphorylated Tau protein (PPTau) is the hallmark of tauopathic neurodegeneration. During "synthetic torpor" (ST), a transient hypothermic state which can be induced in rats by the local pharmacological inhibition of the Raphe Pallidus, a reversible brain Tau hyperphosphorylation occurs. The aim of the present study was to elucidate the - as yet unknown - molecular mechanisms underlying this process, at both a cellular and systemic level. Methods: Different phosphorylated forms of Tau and the main cellular factors involved in Tau phospho-regulation were assessed by western blot in the parietal cortex and hippocampus of rats induced in ST, at either the hypothermic nadir or after the recovery of euthermia. Pro- and anti-apoptotic markers, as well as different systemic factors which are involved in natural torpor, were also assessed. Finally, the degree of microglia activation was determined through morphometry. Results: Overall, the results show that ST triggers a regulated biochemical process which can dam PPTau formation and favor its reversibility starting, unexpectedly for a non-hibernator, from the hypothermic nadir. In particular, at the nadir, the glycogen synthase kinase-β was largely inhibited in both regions, the melatonin plasma levels were significantly increased and the antiapoptotic factor Akt was significantly activated in the hippocampus early after, while a transient neuroinflammation was observed during the recovery period. Discussion: Together, the present data suggest that ST can trigger a previously undescribed latent and regulated physiological process, that is able to cope with brain PPTau formation.

Improvement of the Seminal Characteristics in Rams Using Agri-Food By-Products Rich in Phytomelatonin

The aim of this study was to evaluate the effect of a phytomelatonin-rich diet, including by-products from the food industry, on ram sperm quality and seminal plasma composition. Melatonin content in several by-products before and after in vitro ruminal and abomasal digestion was determined by HPLC-ESI-MS/MS. Finally, 20% of a mix of grape pulp with pomegranate and tomato pomaces was included in the rams' diet, constituting the phytomelatonin-rich diet. Feeding the rams with this diet resulted in an increase in seminal plasma melatonin levels compared with the control group (commercial diet) in the third month of the study. In addition, percentages higher than those in the control group of morphologically normal viable spermatozoa with a low content of reactive oxygen species were observed from the second month onwards. However, the antioxidant effect does not seem to be exerted through the modulation of the antioxidant enzymes since the analysis of the activities of catalase, glutathione reductase and glutathione peroxidase in seminal plasma revealed no significant differences between the two experimental groups. In conclusion, this study reveals, for the first time, that a phytomelatonin-rich diet can improve seminal characteristics in rams.

Perioperative transcutaneous electrical acupoint stimulations as part of an enhanced recovery after surgery protocol for living donors undergoing nephrectomy: A randomized, controlled clinical trial

ObjectiveLiving kidney donors (LKDs) experience perioperative anxiety. We designed the following study to evaluate the anxiolytic effect of transcutaneous electrical acupoint stimulation (TEAS) during the perioperative period in a group of LKDs undergoing laparotomy nephrectomy. MethodsLKDs were randomly assigned to either the TEAS or control group. Participants in the TEAS group received 30min of intervention (6–15 mA, 2–100 Hz), at Yintang (EX-HN-3), bilateral Taichong (LR3) and Neiguan (PC6) one day before surgery (D0), before induction of anesthesia (D1) and one day after surgery (D2). The participants in the control group received the same placement of electrodes but without electrical stimulation. Venous blood was collected before each intervention. Anxiety levels and recovery profiles were recorded. ResultsLKDs in the TEAS group had lower anxiety level than those in the control group at D1, D2 and three days after surgery (D3). The percentage differences were: 33.3%, 25.0%, and 22.2%; [95% confidence interval (CI), (−55.1%, −11.6%), (−47.4%, −2.6%), and (−42.3%, −2.2%); P = 0.005, P = 0.034, and P = 0.035; respectively]. LKDs who received TEAS had better sleep quality and short-term recovery profiles than those in the control group. The plasma levels of 5-hydroxytryptamine (5-HT) and melatonin (MT) in the TEAS group were significantly higher than those in the control group at D1 and D2 (5-HT: P = 0.001, and P < 0.001; MT: P = 0.006, and P = 0.001). At the 3-month follow up, fewer LKDs in the TEAS group had incisional pain when compared to the control group (P = 0.032). ConclusionsPerioperative TEAS decreased perioperative anxiety and facilitated postoperative recovery in the LKDs, and potential decreased the development of chronic pain. Trial Registration: Registered at ChiCTR2000029891, http://www.chictr.org.cn/listbycreater.aspx.

The dim light melatonin onset across ages, methodologies, and sex and its relationship with morningness/eveningness.

The onset of melatonin secretion, the dim light melatonin onset (DLMO), is a tool for determining the phase of the circadian timing system. Although small studies have investigated the impacts of age and methods of calculating DLMO, there is no DLMO reference range. In the current study, the saliva DLMO from 3579 participants from 121 published studies and plasma DLMO from 818 healthy controls from 31 studies (aged 3-73 years) were analyzed. In a subset of 53 papers (1749 participants), individual saliva DLMO and Morningness Eveningness Questionaire (MEQ) scores were obtained from authors or mined from publications and a reference range was constructed. Saliva DLMO was earliest in children to 10 years of age and latest around 20 years of age and thereafter advanced with age by 30 min in the oldest participants. Melatonin assay methods and DLMO calculation methods had little effect on the determination of the DLMO. Saliva DLMO was correlated (p < 0.001) with the MEQ score; lower MEQ scores were associated with later DLMO. MEQ scores increased with age, reflecting a tendency toward morningness. An evaluation of 14 saliva DLMO studies of clinically diagnosed patients living with delayed sleep-wake phase disorder (mean ages 20 to 31 years) revealed mean saliva DLMO within the reference range albeit at the late extreme. Peak plasma melatonin levels from 179 studies of healthy participants revealed a high degree of variability within studies and age groups, but only a small decline between the 20 and 50 years and lowest levels after 70 years.

Role of Melatonin in Daily Variations of Plasma Insulin Level and Pancreatic Clock Gene Expression in Chick Exposed to Monochromatic Light.

To clarify the effect of monochromatic light on circadian rhythms of plasma insulin level and pancreatic clock gene expression and its mechanism, 216 newly hatched chicks were divided into three groups (intact, sham operation and pinealectomy) and were raised under white (WL), red (RL), green (GL) or blue (BL) light for 21 days. Their plasma and pancreas were sampled at six four-hour intervals. For circadian rhythm analysis, measurements of plasma melatonin, insulin, and clock gene expression (cClock, cBmal1, cBmal2, cCry1, cCry2, cPer2, and cPer3) were made. Plasma melatonin, insulin, and the pancreatic clock gene all expressed rhythmically in the presence of monochromatic light. Red light reduced the mesor and amplitude of plasma melatonin in comparison to green light. The mesor and amplitude of the pancreatic clock gene in chickens exposed to red light were dramatically reduced, which is consistent with the drop in plasma melatonin levels. Red light, on the other hand, clearly raised the level of plasma insulin via raising the expression of cVamp2, but not cInsulin. After the pineal gland was removed, the circadian expressions of plasma melatonin and pancreatic clock gene were significantly reduced, but the plasma insulin level and the pancreatic cVamp2 expression were obviously increased, resulting in the disappearance of differences in insulin level and cVamp2 expression in the monochromatic light groups. Therefore, we hypothesize that melatonin may be crucial in the effect of monochromatic light on the circadian rhythm of plasma insulin level by influencing the expression of clock gene in chicken pancreas.

Melatonin Treatment of Circadian Rhythm Sleep-Wake Disorder in Obese Children Affects the Brain-Derived Neurotrophic Factor Level.

Previous studies proved that the brain-derived neurotrophic factor (BDNF) is correlated with sleep regulation, yet how BDNF functions and reacts in the melatonin treatment of circadian rhythm sleep-wake disorder (CRSWD) among obese children remain enigmatic. Focusing on CRSWD in obese children, this study monitored their sleep efficiency and serum BDNF level changes during the treatment of melatonin. In total, 35 obese children diagnosed with CRSWD were included in this study and administrated melatonin (3 mg/night) for 3 months. Blood samples were collected 24 hours before and after the treatment (08:00, 12:00, 16:00, 20:00, 24:00, and 04:00). Subsequently, the plasma melatonin level and serum BDNF level were measured by enzyme-linked immunosorbent assay. Sleep parameters, including sleep quality, Pittsburgh Sleep Quality Index as well as melatonin and BDNF levels before and after treatment, were recorded to profile the effectiveness and safety of melatonin treatment. Melatonin treatment increased plasma melatonin concentration and restored circadian rhythm. Besides, the serum BDNF level showed a significant increase, representing a strong positive correlation with melatonin concentration (p = 0.026). Patients experienced much-improved sleep efficiency (P < 0.001), with longer actual sleep time (P < 0.001), shorter sleep onset latency, and fewer awakenings after treatment (P < 0.001). Besides, melatonin was well tolerated by patients without producing severe side effects. Melatonin treatment effectively improved CRSWD among obese children with their serum BDNF levels increased, indicating that BDNF is a key regulator in CRSWD in obese children. This study may offer theoretical support for melatonin treatment of CRSWD in obese children.

Remote ischemic preconditioning-induced late cardioprotection: possible role of melatonin-mitoKATP-H2S signaling pathway.

Remote ischemic preconditioning (RIPC) confers cardioprotection against ischemia reperfusion (IR) injury. However, the precise mechanisms involved in RIPC-induced cardioprotection are not fully explored. The present study was aimed to identify the role of melatonin in RIPC-induced late cardioprotective effects in rats and to explore the role of H2S, TNF-α and mitoKATP in melatonin-mediated effects in RIPC. Wistar rats were subjected to RIPC in which hind limb was subjected to four alternate cycles of ischemia and reperfusion of 5 min duration by using a neonatal blood pressure cuff. After 24 h of RIPC or ramelteon-induced pharmacological preconditioning, hearts were isolated and subjected to IR injury on the Langendorff apparatus. RIPC and ramelteon preconditioning protected the hearts from IR injury and it was assessed by a decrease in LDH-1, cTnT and increase in left ventricular developed pressure (LVDP). RIPC increased the melatonin levels (in plasma), H2S (in heart) and decreased TNF-α levels. The effects of RIPC were abolished in the presence of melatonin receptor blocker (luzindole), ganglionic blocker (hexamethonium) and mitochondrial KATP blocker (5-hydroxydecanoic acid). RIPC produce delayed cardioprotection against IR injury through the activation of neuronal pathway, which may increase the plasma melatonin levels to activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2S levels. Ramelteon-induced pharmacological preconditioning may also activate the cardioprotective signaling pathway involving the opening of mitochondrial KATP channels, decrease in TNF-α production and increase in H2S levels.

Изменения микробиоты кишечника у больных ювенильным идиопатическим артритом

Currently, the issue of the relationship between gut microbiota and juvenile idiopathic arthritis (JIA) is still relevant. The study was aimed to assess alterations in the gut microbiota taxonomic composition and estimate the relationship between these alterations and cortisol, melatonin, and TNFα at the genus level in patients with JIA. The comparative cross-sectional study involved 65 patients with JIA (index group) and 60 healthy children (control group). The gut microbiota taxonomic composition and plasma levels of cortisol, melatonin, and TNFα were assessed. The following alterations of the gut microbiota taxonomic composition were found in patients with JIA: the significantly decreased abundance of Anaerostipes (р = 0.042), Lachnospira (р = 0.034), Roseburia (р = 0.002), Coprococcus (р = 0.014), Dialister (р = 0.003) and the increase in the abundance of Ruminococcus (р = 0.012). There were significant correlations of cortisol levels with the abundance of Lachnospira (r = –0.44; p = 0.001), melatonin concentrations and the abundance of Coprococcus (r = –0.48; p = 0.023), the levels of TNFα and the abundance of Ruminococcus (r = 0.52; p = 0.001). The association of the Lachnospira, Roseburia, and Ruminococcus abundance with the higher DAS28 scores was discovered (r = –0.57; p = 0.002; r = –0.44; p = 0.002; r = 0.54; p = 0.032, respectively). The findings provide additional information about the features of gut microbiota alterations and their correlation with some hormone and inflammatory biomarkers associated with JIA, that could provide the basis for further research and possibly for new approaches to treatment of this disorder.

Blast Exposure Dysregulates Nighttime Melatonin Synthesis and Signaling in the Pineal Gland: A Potential Mechanism of Blast-Induced Sleep Disruptions.

Blast-induced traumatic brain injury (bTBI) frequently results in sleep-wake disturbances. However, limited studies have investigated the molecular signaling mechanisms underlying these sleep disturbances, and potentially efficacious therapies are lacking. We investigated the levels of melatonin and genes involved in melatonin synthesis pathway in the pineal glands of Sprague Dawley rats exposed to single and tightly coupled repeated blasts during the night and daytime. Rats were exposed to single and tightly coupled repeated blasts using an advanced blast simulator. The plasma, cerebrospinal fluid (CSF), and pineal gland were collected at 6 h, 24 h, or 1 month postblast at two different time points: one during the day (1000 h) and one at night (2200 h). Differential expressions of genes involved in pineal melatonin synthesis were quantified using quantitative real-time polymerase chain reaction (qRT-PCR). Plasma and CSF melatonin levels were assessed using a commercial melatonin ELISA kit. The plasma and CSF melatonin levels showed statistically significant decreases at 6 h and 24 h in the blast-exposed rats euthanized in the night (in dim light), with no significant alterations noted in rats euthanized in the morning (daylight) at all three-time points. Blast-exposed rats showed statistically significant decreases in Tph1, Aanat, Asmt, and Mtnr1b mRNA levels, along with increased Tph2 mRNA, in the pineal gland samples collected at night at 6 h and 24 h. No significant changes in the mRNA levels of these genes were noted at 1 month. These findings imply that the melatonin circadian rhythm is disrupted following blast exposure, which may be a factor in the sleep disturbances that blast victims frequently experience.

The Effect of Zinc Supplementation on Plasma Melatonin and Kisspeptin Levels in Rams

The study that researched the effect of zinc added to the rations of rams on kisspeptin and melatonin levels was conducted on 2 years old 12 Kivircik crossbreed rams (6 control, 6 experimental) for 1 year. In addition to the ad libitum dry alfalfa straw, it was given mixed feed (barley, salt and vitamin-mineral mixture as standard) supplemented with 25 mg/kg/ DM ZnO, for the control group and 125 mg/kg/ DM ZnO for experimental group per day. During the study, blood samples were taken once a month and kisspeptin and melatonin levels were measured with ELISA in plasmas obtained from blood samples. Melatonin levels were found to be between 62.8-164.5 ng/L in experimental group and 22.1-105.9 ng/L in control group. Kisspeptin levels were determined to be between 209.8-514.2 ng/L in experimental group and 92.6-356.6 ng/L in control group. Zinc supplementations showed numerical increases in kisspeptin and melatonin levels but because of the individual variations, no statistical significance was found (P &gt; 0.05).

Effects of Extreme Light Cycle and Density on Melatonin, Appetite, and Energy Metabolism of the Soft-Shelled Turtle (Pelodiscus sinensis).

Simple SummaryLight is an important factor that affects a variety of physiological functions of animals. Melatonin is known as the hormonal mediator of photoperiodic information to the central nervous system in vertebrates and plays a key role in food intake and energy balance regulation. The present work aimed to examine the effect of extreme light cycles (herein meaning constant darkness and constant light) that animals may encounter under dark culture situations or light pollution on melatonin secretion and melatonin-modulated appetite and energy metabolism of the soft-shelled turtle Pelodiscus sinensis. We measured melatonin level, appetite, and energy metabolism-related parameters under various photoperiods and stocking densities during daytime and nighttime. The results demonstrated that (1) melatonin secretion of the turtle was not only affected by light, but also likely to be regulated by unknown endogenous factors and density; and (2) altered plasma melatonin induced by constant darkness and density seemed to be involved in the modulation of energy metabolism (elevated thyroid activity and standard metabolic rate) rather than appetite (unchanged leptin and ghrelin contents, kisspeptin 1, cocaine amphetamine-regulated transcript, and neuropeptide Y mRNA) in Chinese soft-shelled turtles. Our results shed light on the physiological responses of freshwater turtles to extreme light cycles and also contribute important data for turtle culture.Constant darkness and constant light exposure often disturb the circadian rhythm in the behavior and energy metabolism of vertebrates. Melatonin is known as the hormonal mediator of photoperiodic information to the central nervous system and plays a key role in food intake and energy balance regulation in vertebrates. The popularly cultured soft-shelled turtle Pelodiscus sinensis has been reported to grow better under constant darkness; however, the underlying physiological mechanism by which darkness benefits turtle growth is not clear yet. We hypothesized that increased melatonin levels induced by darkness would increase appetite and energy metabolism and thus promote growth in P. sinensis. In addition, in order to elucidate the interaction of photoperiod and density, juvenile turtles were treated under three photoperiods (light/dark cycle: 24L:0D, 12L:12D, 0L:24D, light density 900 lux) and two stocking densities (high density: 38.10 ind./m2, low density: 6.35 ind./m2) for 4 weeks, and then the blood and brain tissues of turtles were collected during the day (11:00–13:00) and at night (23:00–1:00) after 2 days of fasting. We examined changes in plasma melatonin levels, food intake (FI), and appetite-related hormones (plasma ghrelin and leptin), as well as growth and energy metabolism parameters such as specific growth rate (SGR), standard metabolic rate (SMR), plasma growth hormone (GH), and thyroid hormone/enzyme activity (plasma triiodothyronine T3, thyroxine T4, and T45′-deiodinase activity). Moreover, we also assessed the responses of mRNA expression levels of food intake-related genes (kisspeptin 1 (Kiss1); cocaine amphetamine-regulated transcript (CART); neuropeptide Y (NPY)) in the brain. The results showed that under high density, SGR was the lowest in 24L:0D and the highest in 0L:24D. FI was the highest in 0L:24D regardless of density. Plasma melatonin was the highest in 0L:24D under high density at night. SMR increased with decreasing light time regardless of density. Most expressions of the measured appetite-related genes (Kiss1, CART, and NPY) were not affected by photoperiod, nor were the related hormone levels, such as plasma leptin, ghrelin, and GH. However, thyroid hormones were clearly affected by photoperiod. T3 level in 0L:24D under high density during the day was the highest among all treatment groups. T4 in 24L:0D under high density during the day and T45′-deiodinase activity in 24L:0D under low density at night were significantly reduced compared with the control. Furthermore, the energy metabolism-related hormone levels were higher under higher density, especially during the day. Together, melatonin secretion is not only modulated by light but also likely to be regulated by unknown endogenous factors and density. Altered plasma melatonin induced by constant darkness and density seems to be involved in the modulation of energy metabolism rather than appetite in the soft-shelled turtle.

Abstract 222: Exposure to dim light at night disrupts the nocturnal melatonin signal in male nude rats bearing tissue-isolated castration-sensitive VCaP human prostate cancer: Impact on tumor circadian dynamics of the Warburg effect, lipid signaling and proliferation

Abstract Over 248,000 men in the U.S. alone this year will be diagnosed with prostate cancer, and over 33,300 will die from the disease. The World Health Organization, in the case of breast cancer, has classified night-shift work involving light at night (LAN)-induced circadian disruption to be a probable carcinogen (Class 2A). Exposure to LAN suppresses nighttime pineal melatonin (MLT) production that influences normal and neoplastic tissue metabolism, physiology, and proliferation. Previously, we showed in rodent and human tumors in vivo that MLT inhibits linoleic acid (LA)-uptake and conversion to 13-hydroxyoctadecadienoic acid (13-HODE), a lipoxygenase product that enhances epidermal growth factor and insulin-like growth factor-I-induced mitogenesis. Recently, we developed a tissue-isolated, castration-sensitive VCaP human prostate cancer xenograft model to test the hypothesis that suppression of the nocturnal MLT signal due to exposure to dim LAN (dLAN) accelerates tumor LA-uptake and metabolism, aerobic glycolysis (Warburg Effect), and proliferative activity. Male nude rats (Crl:NIHFoxn1rnu; n=6/group) bearing castration-sensitive VCaP human prostate cancer xenografts were maintained on either a control L(300 lux)D(0 lux),12:12 or experimental LD,12:12dLAN (300 lux light phase followed by dLAN 0.2 lux dark phase intensity) light/dark cycle. Results revealed (Mean ± S.D.) plasma MLT levels in controls peaked in the mid-dark phase (183.4 ± 12.8 pg/mL) and were lowest (2.2 ± 0.4 pg/mL) in the mid-light phase, and low (&amp;lt; 10 pg/mL) throughout the 24-hr period in dLAN rats. Tumors in rats exposed to dLAN exhibited a significantly shorter latency to onset and a two-fold faster growth rate than controls. Harvested control group tumors revealed elevated cAMP levels, LA uptake, 13-HODE production, the Warburg effect, and [3H]thymidine incorporation into DNA, as well as elevated patterns of expression of signaling pathways phospho-ERK1/2, -AKT, -STAT3, -glycogen synthase kinase-3β (GSK3β), and -NF-κβ, and full-length androgen receptor and aldo-keto reductase (AKR1C3), during the light phase and markedly suppressed during the dark phase. In the dLAN group, these measures were markedly elevated throughout the 24-hr period. This is the first evidence in vivo, that dLAN-induced disruption of integrated circadian rhythms of signaling, metabolism, and proliferation results in accelerated growth of castration-sensitive human prostate cancer xenografts. Thus, lighting design strategies to minimize human exposure to LAN that preserve the integrity of the circadian MLT signal may offer a novel approach to suppress the growth progression of human castration-sensitive prostate cancer in our increasingly 24-hour society. Citation Format: Erin M. Dauchy, Robert T. Dauchy, Steven M. Hill, Yan Dong, Victoria P. Belancio, Shulin Xiang, George C. Brainard, John P. Hanifin, David E. Blask. Exposure to dim light at night disrupts the nocturnal melatonin signal in male nude rats bearing tissue-isolated castration-sensitive VCaP human prostate cancer: Impact on tumor circadian dynamics of the Warburg effect, lipid signaling and proliferation [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 222.

Modulation of melatonin to the thalamic lesion-induced pain and comorbid sleep disturbance in the animal model of the central post-stroke hemorrhage

The devastating chronic central post stroke pain is associated with variety of comorbidities. Disrupted sleep is a severe comorbidity, causing an increase in the suicide rate, due to CPSP’s pain symptom. Melatonin is a well-known jet-lag compound, which helps in entrainment of sleep cycle. Accordingly, whether melatonin as a therapeutic measurement for the regulation of sleep disturbance related to central post stroke pain remains unclear. Exogenous melatonin administration entrained the disrupted 24 h circadian cycle, more effectively after 2 and 3 week of administration. The effect of melatonin was persisted on 4th week too, when melatonin administration was discontinued. Also, melatonin ameliorated the pain due to distorted sleep-activity behavior after melatonin administration for 3 weeks. The low levels of melatonin in blood plasma due to CPSP were restored after 3 weeks of melatonin administration. After 30 mg/kg melatonin administrations for 3 weeks, all the disrupted resting and activity behaviors were reduced during light and dark periods. The results suggested that melatonin significantly ameliorated CPSP’s pain symptoms and comorbid sleep disturbance showing in activity behavior.

Hibernation with Rhythmicity in the Retina, Brain, and Plasma but Not in the Liver of Hibernating Giant Spiny Frogs (Quasipaa spinosa).

Simple SummaryAquatic ectotherms experience hypoxia under water during hibernation, which enables them to move denoting some level of consciousness, unlike terrestrial hibernators. However, how aquatic ectotherms modulate their clocks and clock-controlled genes in different tissues and plasma melatonin and corticosterone in light-dark cycles under natural environments before and during hibernation, remains to be largely unexplored. To achieve these, in this study, we investigated circadian clock genes, circadian clock-controlled genes, antioxidant enzyme genes, and related hormones in giant spiny frog (Quasipaa spinosa). Our results demonstrated that, despite the hypometabolic state of hibernation, the retina and the brain displayed some circadian rhythms of clock and antioxidant genes, as well as melatonin, while the liver was inactive. These novel findings may contribute to an understanding of how aquatic ectotherms use their circadian system differentially to modulate their physiology in escaping hypoxia during hibernation and preparing for arousal.Hibernation in ectotherms is well known, however, it is unclear how the circadian clock regulates endocrine and antioxidative defense systems of aquatic hibernators. Using the giant spiny frog (Quasipaa spinosa), we studied mRNA expression levels of (1) circadian core clock (Bmal1, Clock, Cry1 and Per2), clock-controlled (Ror-α, Mel-1c and AANAT), and antioxidant enzyme (AOE) (SOD1, SOD2, CAT and GPx) genes in retina, brain, and liver; and (2) plasma melatonin (MT) and corticosterone (CORT) levels, over a 24-hour period at six intervals pre-hibernation and during hibernation. Our results showed that brain Bmal1, Cry1, Per2 and Mel-1c were rhythmic pre-hibernation and Clock and Ror-α during hibernation. However, the retina Bmal1, Clock and Mel-1c, and plasma MT became rhythmic during hibernation. All brain AOEs (SOD1, SOD2, CAT and GPx) were rhythmic pre-hibernation and became non-rhythmic but upregulated, except SOD1, during hibernation. However, plasma CORT and liver clocks and AOEs were non-rhythmic in both periods. The mRNA expression levels of AOEs closely resembled those of Ror-α but not plasma MT oscillations. In the hibernating aquatic frogs, these modulations of melatonin, as well as clock and clock-controlled genes and AOEs might be fundamental for them to remain relatively inactive, increase tolerance, and escape hypoxia, and to prepare for arousal.

Melatonin dose: testicular and testosterone response in Border Leicester rams during spring

The negative effects of seasonality on ram fertility during the spring months (non-breeding season) can be addressed by administration of melatonin. Slow-release implants containing 18 mg of melatonin are available to improve reproductive responses in ewes but as far as we are aware nobody has examined the effects of dose on increasing testicular size and plasma testosterone levels. Mature Border Leicester rams were randomly allocated to four doses (0, 18, 36 and 54 mg) with treatment beginning in mid-September (spring). Measurements (scrotal size, testosterone and melatonin concentrations, live weight and body condition score) began before hormone administration and continued at monthly intervals until January (mid-summer). Scrotal circumference increased with increasing dose with 36 and 54 mg treatments producing larger responses than 0 and 18 mg treatments (p < 0.05). Plasma testosterone concentration was positively related (p ≤ 0.05) with plasma melatonin levels on days 60 and 90 after melatonin administration. There was a negative relationship (p < 0.01) between plasma melatonin concentration and liveweight on day 30. It is concluded that a higher dose of melatonin is required to maintain plasma melatonin levels in larger animals, and that at least 36 mg is required to elicit a threshold response in testicular size.

Anatomical and histological investigation of the pineal gland in the lake van fish (Alburnus tarichi (Güldenstädt, 1814)).

The pineal gland and melatonin secreted from the gland regulate the biological clock and adaptation to seasonal changes, glucose balance, nutrition and locomotor activities. In this study, the pineal gland of the Lake Van fish was examined anatomically and histologically. The melatonin level secreted from the pineal gland was determined in fish plasma sampled from both lakes and streams during reproduction migration. The pineal gland in the Lake Van fish, as in other teleost fish, is located in the head, under the translucent pineal window, which does not contain many pigment cells. The gland consists of pineal vesicle and pineal stalk parts on the dorsal sac in the Lake Van fish. It was determined that the pineal gland showed good vascularity. The presence of pinealocytes and different types of cells in the pineal organ was determined histologically. Pinealocytes were intensely localized in the lumen of the pineal vesicle. The plasma melatonin level increased in fish passing from lake to stream for reproductive migration.