Effects of 12 Weeks of Daily Melatonin Administration on Inflammatory Markers and Adipose Tissue Mass of Rats under Hypoestrogenism.

Background and Objectives: The hormonal state of hypoestrogenism is associated with the accumulation of white adipose tissue, which can induce an increase in pro-inflammatory markers, leading to progressive health complications. Melatonin can act on adipose tissue mass, promoting its reduction and influencing inflammation, reducing IL-6 and releasing IL-10, pro- and anti-inflammatory markers, respectively. However, the role of melatonin regarding such parameters under the context of hypoestrogenism remains unknown. The aim of this study was to determine the effect of 12 weeks of hypoestrogenism and melatonin on white adipose tissue mass and circulating levels of IL-6, IL-10, TGF-ß-1, and leukotriene C4 (LTC4). Materials and Methods: The animals (Wistar rats with sixteen weeks of age at the beginning of the experiment) under hypoestrogenism were submitted to the surgical technique of bilateral ovariectomy. The animals received melatonin (10 mg·kg-1) or vehicles by orogastric gavage every day for 12 weeks and administration occurred systematically 1 h after the beginning of the dark period. White adipose tissue (perigonadal, peritoneal, and subcutaneous) was collected for mass recording, while blood was collected for the serum determination of IL-6, IL-10, TGF-ß-1, and LTC4. Results: Hypoestrogenism increased the perigonadal and subcutaneous mass and IL-6 levels. Melatonin kept hypoestrogenic animals in physiological conditions similar to the control group and increased thymus tissue mass. Conclusions: Hypoestrogenism appears to have a negative impact on white adipose tissue mass and IL-6 and although melatonin commonly exerts a significant effect in preventing these changes, this study did not have a sufficiently negative impact caused by hypoestrogenism for melatonin to promote certain benefits.

Can supplementation of tryptophan in parenteral nutrition increase melatonin and alleviate inflammatory response?

OBJECTIVE: Endogenous melatonin is produced from tryptophan which is an essential amino acid. Besides its role in the regulation of sleep patterns, melatonin has anti-inflammatory effects. In this case-control study, we aimed to compare tryptophan and melatonin levels and their relationship with the inflammatory response, specifically serum interleukin-1, interleukin-6, and c-reactive protein levels following major abdominal surgery in patients with food restriction and who receive parenteral nutritional therapy. METHODS: We enrolled 40 patients between the ages of 18 and 65 years in the study. We collected blood and urine samples 48 h before the operation and on postoperative days 1, 3, and 5. RESULTS AND CONCLUSION: The tryptophan levels in the experimental group were higher than in the control group but failed to reach any statistical difference. Melatonin levels were increased in both groups following the surgery compared with preoperative levels. The increase in the experimental group was statistically different 3 days after the surgery. The difference in the level of interleukin-1 between the control and the experimental groups was greatest on postoperative day 3. On postoperative day 3, the interleukin-6 level in the treatment group was slightly higher than in the control group. We did not find any difference in the levels of c-reactive protein between the groups. As a result, the levels of tryptophan and melatonin were increased in the parenteral nutrition group, irrespective of the postoperative inflammatory response.

Parameters of Oxidative Stress, Vitamin D, Osteopontin, and Melatonin in Patients with Lip, Oral Cavity, and Pharyngeal Cancer.

Lip, oral cavity, and pharyngeal cancers (LOCP) constitute a group of rare neoplasms with unfavorable prognosis. So far, not much is known about the role of vitamin D and oxidative stress in the pathogenesis of LOCP in the European population. The aim of the study was to determine the concentrations of vitamin D, osteopontin, melatonin, and malondialdehyde (MDA) as markers of oxidative stress and/or inflammation, as well as the activities of antioxidant enzymes in the course of LOCP. The vitamin D, melatonin, and osteopontin concentrations in blood serum, the MDA levels in erythrocytes and blood plasma, and the activities of superoxide dismutase (SOD-1), catalase (CAT), and glutathione peroxidase (GPx) in erythrocytes were measured in blood samples taken from 25 LOCP patients of middle age (YCG), 20 LOCP elderly patients (OCG), and 25 healthy middle-aged volunteers. In both cancer groups, decreases in vitamin D and CAT, as well as increases in osteopontin and blood plasma MDA, were observed. An increase in GPx activity in YCG and a decrease in melatonin level in OCG were found. The results indicate the vitamin D deficiency and disturbed oxidant-antioxidant homeostasis in LOCP patients. Osteopontin seems to be associated with LOCP carcinogenesis and requires further research.

Changes in endogenous daytime melatonin levels after aneurysmal subarachnoid hemorrhage - Preliminary findings from an observational cohort study.

INTRODUCTION: Aneurysmal subarachnoid hemorrhage (aSAH) is associated with early and delayed brain injury due to several underlying and interrelated processes, which include inflammation, oxidative stress, endothelial, and neuronal apoptosis. Treatment with melatonin, a cytoprotective neurohormone with anti-inflammatory, anti-oxidant and anti-apoptotic effects, has been shown to attenuate early brain injury (EBI) and to prevent delayed cerebral vasospasm in experimental aSAH models. Less is known about the role of endogenous melatonin for aSAH outcome and how its production is altered by the pathophysiological cascades initiated during EBI. In the present observational study, we analyzed changes in melatonin levels during the first three weeks after aSAH. MATERIALS AND METHODS: Daytime (from 11:00 am to 05:00 pm) melatonin levels were measured by enzyme-linked immunosorbent assay (ELISA) in serum samples obtained from 30 patients on the day of aSAH onset (d0) and in five pre-defined time intervals during the early (d1-4), critical (d5-8, d9-12, d13-15) and late (d16-21) phase. Perioperative daytime melatonin levels determined in 30 patients who underwent elective open aortic surgery served as a control for the acute effects of surgical treatment on melatonin homeostasis. RESULTS: There was no difference between serum melatonin levels measured in the control patients and on the day of aSAH onset (p = 0.664). However, aSAH was associated with a sustained up-regulation that started during the critical phase (d9-12) and progressed to the late phase (d16-21), during which almost 80% of the patients reached daytime melatonin levels above 5 pg/ml. In addition, subgroup analyses revealed higher melatonin levels on d5-8 in patients with a poor clinical status on admission (p = 0.031), patients with anterior communicating artery aneurysms (p = 0.040) and patients without an external ventricular drain (p = 0.018), possibly pointing to a role of hypothalamic dysfunction. CONCLUSION: Our observations in a small cohort of patients provide first evidence for a delayed up-regulation of circulatory daytime melatonin levels after aSAH and a role of aneurysm location for higher levels during the critical phase. These findings are discussed in terms of previous results about stress-induced melatonin production and the role of hypothalamic and brainstem involvement for melatonin levels after aSAH.

Effects of general versus subarachnoid anaesthesia on circadian melatonin rhythm and postoperative delirium in elderly patients undergoing hip fracture surgery: A prospective cohort clinical trial.

BACKGROUND: Circadian rhythm disturbance is common postoperatively in older patients with hip fractures, which may contribute to the development of postoperative delirium (POD). As a reliable biomarker of endogenous circadian rhythms, melatonin regulates the sleep-wake cycle and environmental adaptation, and its secretory rhythm may be modified by anaesthesia and surgery. This study compared the impact of subarachnoid anaesthesia (SA) and general anaesthesia (GA), on the peak of melatonin secretion (primary outcome), the circadian rhythm of melatonin, cortisol and sleep, and the POD incidence (secondary outcome). METHODS: In this prospective cohort observational study, hip fracture surgery patients were enrolled and assigned to receive either SA or GA. Postoperative plasma melatonin and cortisol levels were dynamically measured every six hours on seven time-points, and the circadian rhythm parameters including mesor, amplitude, and acrophase were calculated. Subjective and objective sleep assessments were performed by sleep diaries and sleep trackers, respectively. The Confusion Assessment Method was used twice daily by a specific geriatrician to screen for POD occurrence. FINDINGS: In a cohort of 138 patients who underwent hip fracture surgery, the circadian rhythm disruption of the patients in the GA group (n=69) was greater than the SA group (n=69). Compared with SA, GA provided the lower peak concentration, mesor, and amplitude of melatonin secretion on postoperative day 1 (p < 0.05). Patients in the GA group experienced higher awakenings, more sleep deprivation, and poor sleep quality on surgery day (p < 0.05). A proportion of 12 patients in the SA group (17.4%) and 24 patients in the GA group (34.8%) experienced POD (p = 0.020). INTERPRETATION: These results suggest that SA may be superior to GA in elderly patients undergoing hip fracture surgery as SA is associated with less impairment of the melatonin rhythm and sleep patterns, and fewer POD occurrences. FUNDING: The study was supported by the National Natural Science Foundation of China (81971012, 81873726, 81901095, 81701052, and 81801070), Key Clinical Projects of Peking University Third Hospital (BYSYZD2019027), and Peking University "Clinical Medicine plus X" Youth Project (PKU2020LCXQ016).

Salivary melatonin in oral squamous cell carcinoma patients.

Melatonin's role in circadian rhythm is well documented, as are its' anti-oxidant, oncostatic and anti-inflammatory properties. Poor sleep quality has been associated as a potential risk factor for several malignancies, including head and neck cancers. The purpose of this study is to determine salivary melatonin (MLT) levels in oral squamous cell carcinoma (OSCC) patients, compare the salivary MLT levels with those in healthy individuals and compare the salivary and serum levels in OSCC patients. Furthermore, the aim is to investigate the potential relationship between sleep quality and salivary MLT levels in OSCC patients. Unstimulated (UWS) and stimulated (SWS) whole saliva was sampled from patients with T1N0M0 and T2N0M0 OSCC (N = 34) and 33 sex and age matched healthy subjects. Serum samples were taken from 11 OSCC patients. Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) questionnaire. Melatonin levels in UWS and SWS were significantly higher in the OSCC group. Sleep quality was significantly lower in patients with OSCC (P = 0.0001). ROC analysis was found to be significant (P < 0.001) in evaluating MLT concentration limit in diagnosing OSCC. The expected relationship between sleep quality and salivary MLT levels in OSCC patients was not observed. Our results suggest salivary MLT as a potential biomarker that might facilitate non-invasive detection of early stage OSCC.

Melatonin Alleviates Acute Gouty Inflammation In Vivo and In Vitro.

The aim of this study was to identify the effects of melatonin on acute gouty inflammation and to investigate the underlying mechanisms. We found significantly lower serum melatonin levels in gout patients in the acute phase than in those in the remission phase or in normal individuals. The mRNA expression of melatonin receptor 2 (MT2) was also lower in gout patients than in normal individuals. To verify the in-vivo role of melatonin, a gouty arthritis model was established by intraarticular injection of monosodium urate (MSU, 1 mg) crystals into the paws of C57BL/6 mice. Joint inflammation in the mouse model was evaluated by measuring the thickness of the right paw/left paw, and the inflammation index was determined by examining infiltrating neutrophils with haematoxylin and eosin (H&E) staining. Melatonin was found to reduce both paw thickness and the inflammation index in the mouse model, and melatonin also reduced the mRNA levels of interleukin-1 beta (IL-1ß), IL-6 and NLR family pyrin domain containing 3 (NLRP3) inflammasome. To mimic gouty inflammation in vitro, mouse peritoneal macrophages were stimulated with lipopolysaccharides (LPS) plus MSU. Melatonin was revealed to reduce IL-1ß secretion by stimulated macrophages. The mRNA expression levels of IL-1ß and IL-6 were also inhibited by melatonin. Western blot analysis showed that the expression of NLRP3, caspase-1 and pro-IL-1ß was also inhibited by melatonin. In conclusion, our study demonstrated that melatonin alleviated gouty inflammation in vivo and in vitro, and the underlying mechanism may involve inhibiting the assembly of the NLRP3 inflammasome.

Myopia, Melatonin and Conjunctival Ultraviolet Autofluorescence: A Comparative Cross-sectional Study in Indian Myopes.

Purpose: To explore the role of outdoor light exposure by estimating ocular sun exposure measured by Conjunctival Ultraviolet Autofluorescence (CUVAF) imaging and serum melatonin levels in myopes and non-myopes.Materials & Methods: Age and sex matched emmetropes and myopes (60 each) aged 10-25 years participated. Those with a history of ocular surgery or any ocular or systemic co-morbidity were excluded. Socio-demographic parameters, sun exposure questionnaires, indoor and outdoor activity profile, morning serum melatonin levels, sleep pattern, degree of myopia, ocular biometry and area of CUVAF on ultraviolet photography were noted and analyzed.Results: Mean age of myopes (18 ± 4.5 years) and emmetropes (18.5 ± 4 years) was similar (P = .523). Serum melatonin levels were significantly higher (P = .001) among myopes (89.45 pg/ml) as compared to emmetropes (52.83 pg/ml). Lifetime sun exposure was significantly lower in myopes than emmetropes (P = .0003). Area of CUVAF was inversely related to degree of myopia (P < .0001). Day time sleepiness was greater in myopes (51.7%) than emmetropes (15%) (P < .0001). There was a positive correlation between serum melatonin levels and axial length among myopes (correlation coefficient = 0.27; P = .03). Age and gender had no association with serum melatonin levels.Conclusion: This study demonstrates an inverse relationship between serum melatonin levels and degree of CUVAF in myopes. A novel link between serum melatonin, axial length and outdoor sun exposure is highlighted in the current study.

Long-term continuous positive airway pressure treatment ameliorates biological clock disruptions in obstructive sleep apnea.

BACKGROUND: Obstructive Sleep Apnea (OSA) is a highly prevalent and underdiagnosed sleep disorder. Recent studies suggest that OSA might disrupt the biological clock, potentially causing or worsening OSA-associated comorbidities. However, the effect of OSA treatment on clock disruption is not fully understood. METHODS: The impact of OSA and short- (four months) and long-term (two years) OSA treatment, with Continuous Positive Airway Pressure (CPAP), on the biological clock was investigated at four time points within 24 h, in OSA patients relative to controls subjects (no OSA) of the same sex and age group, in a case-control study. Plasma melatonin and cortisol, body temperature and the expression levels and rhythmicity of eleven clock genes in peripheral blood mononuclear cells (PBMCs) were assessed. Additional computational tools were used for a detailed data analysis. FINDINGS: OSA impacts on clock outputs and on the expression of several clock genes in PBMCs. Neither short- nor long-term treatment fully reverted OSA-induced alterations in the expression of clock genes. However, long-term treatment was able to re-establish levels of plasma melatonin and cortisol and body temperature. Machine learning methods could discriminate controls from untreated OSA patients. Following long-term treatment, the distinction between controls and patients disappeared, suggesting a closer similarity of the phenotypes. INTERPRETATION: OSA alters biological clock-related characteristics that differentially respond to short- and long-term CPAP treatment. Long-term CPAP was more efficient in counteracting OSA impact on the clock, but the obtained results suggest that it is not fully effective. A better understanding of the impact of OSA and OSA treatment on the clock may open new avenues to OSA diagnosis, monitoring and treatment.

Effects of photoperiod on morphology and function in testis and epididymis of Cricetulus barabensis.

Photoperiod regulates the seasonal reproductive rhythms of mammals by influencing the development and function of sexual organs; however, the underlying mechanism remains unclear. We examined the morphology and functioning of the main sex organs of striped dwarf hamsters (Cricetulus barabensis) under different photoperiods (short daylight [SD], moderate daylight [MD], and long daylight [LD]) and further investigated the underlying molecular mechanisms. There was an inverse correlation between blood melatonin levels and photoperiod in the order SD > MD > LD. Decreases in body and tissue weights were observed under SD, whereas testis and epididymis weights between MD and LD were comparable. The diameters of the spermatogenic tubules, thickness of the spermatogenic epithelium, and the number of spermatogonia and Sertoli cells decreased under SD, whereas the serum-luteinizing hormone, follicle-stimulating hormone, and fecal testosterone concentrations decreased under LD. In SD, bax/bcl2 protein expression increased in the testes and decreased in the epididymides, whereas LC3II/LC3I remained unchanged in the testes and increased in the epididymides compared with the MD group. In LD, bax/bcl2 and LC3II/LC3I protein expression levels were unchanged in the testes but were decreased in the epididymides. In SD and LD, adenosine triphosphate synthase and citrate synthase protein expression levels were unchanged in the testes but were decreased in the epididymides. Drp1 and Mff protein expression increased in the testes and decreased in the epididymides. Overall, different regulatory mechanisms in the testis and epididymis led to degeneration under SD and maintenance under LD, preferentially protecting mitochondrial function in the testis by regulating mitochondrial fission.

Brief Report: Relationship Between Cotinine Levels and Peripheral Endogenous Concentrations of Oxytocin, ß-Endorphin, and Orexin in Individuals With Both Alcohol and Nicotine Use Disorders.

BACKGROUND AND OBJECTIVES: In this secondary analysis of a pilot clinical trial with individuals with alcohol and nicotine use disorders, we investigate the relationship between serum concentrations of oxytocin, ß-endorphin, melatonin, α-melanocyte-stimulating hormone, substance P, and orexin, with objective biomarkers (salivary cotinine and serum γ-glutamyl transferase [GGT]) as well as with self-reported smoking and alcohol drinking. METHODS: Biomarkers for a total of N = 19 participants were analyzed using multiplexed, competitive format immune-assay (peptides) and enzyme competitive immunoassay (saliva). A regression analysis using Pearson's correlation coefficient was utilized to determine correlations. We controlled for multiple comparisons, checked for collinearities, and ran two-sided statistical tests. RESULTS: We found significant positive correlations for cotinine and oxytocin (P = .002), ß-endorphin (P = .008), and orexin (P < .001), but not for either GGT or self-reported smoking or alcohol drinking. CONCLUSION AND SCIENTIFIC SIGNIFICANCE: These preliminary results suggest a relationship between cotinine and oxytocin, ß-endorphin, and orexin, which opens up new potential hypotheses on the potential role of these endocrine pathways in tobacco smokers. (Am J Addict 2021;30:88-91).

Exposure to Radiation During Work Shifts and Working at Night Act as Occupational Stressors Alter Redox and Inflammatory Markers.

BACKGROUND: Studies of breast cancer etiology suggest evidence that night shift working and occupational exposure to ionizing radiation (IR) are defined risk factors for breast cancer development. There are few studies to clarify neuroendocrine and inflammatory status and the possible consequences particularly in occupational exposure. AIM OF THE STUDY: Our aim was to associate the redox and inflammatory biomarkers with either nightshift working or occupational radiation exposure, and to compare their levels between the two groups at Alexandria University Hospitals, Alexandria, Egypt. METHODS: We included 150 female nurses at Alexandria University Hospitals: 50 nightshift workers, 50 radiation workers, and 50 dayshift workers as a control group (neither work nightly nor radiation workers). In morning serum sample (7 am), we measured the concentrations of serum melatonin, Cortisol, tumor necrosis factor-alpha (TNF-α) and interferon-gamma (IFN-γ) by ELISA; malondialdehyde (MDA) and total antioxidant capacity (TAC) levels colorimetrically, and C-reactive protein (C-RP) levels by turbidimetric method. RESULTS: Nightshift workers had significantly lower levels of melatonin and TAC, and higher levels of serum inflammatory markers and cortisol, than day shift control group of workers. Workers occupationally exposed to IR had significantly higher levels of serum melatonin, MDA and inflammatory markers, lower levels of serum cortisol, and lower TAC than day shift workers. CONCLUSION: Occupational exposure to IR and working nightly alter circulating redox and inflammatory biomarkers.

Association between circadian rhythm disruption and polycystic ovary syndrome.

OBJECTIVE: To explore the association of circadian rhythm disruption with polycystic ovary syndrome (PCOS) and the potential underlying mechanism in ovarian granulosa cells (GCs). DESIGN: Multicenter questionnaire-based survey, in vivo and ex vivo studies. SETTING: Twelve hospitals in China, animal research center, and research laboratory of a women's hospital. PATIENTS/ANIMALS: A total of 436 PCOS case subjects and 715 control subjects were recruited for the survey. In vivo and ex vivo studies were conducted in PCOS-model rats and on ovarian GCs collected from women with PCOS and control subjects. INTERVENTION(S): The PCOS rat model was established with the use of testosterone propionate. MAIN OUTCOME MEASURE(S): Assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq), RNA sequencing, rhythmicity analysis, functional enrichment analysis. RESULT(S): There was a significant correlation between night shift work and PCOS. PCOS-model rats presented distinct differences in the circadian variation of corticotropin-releasing hormone, adrenocorticotropic hormone, prolactin, and a 4-h phase delay in thyrotropic hormone levels. The motif enrichment analysis of ATAC-seq revealed the absence of clock-related transcription factors in specific peaks of PCOS group, and RNA sequencing ex vivo at various time points over 24 hours demonstrated the differential rhythmic expression patterns of women with PCOS. Kyoto Encyclopedia of Genes and Genomes analysis further highlighted metabolic dysfunction, including both carbohydrate and amino acid metabolism and the tricarboxylic acid cycle. CONCLUSION(S): There is a significant association of night shift work with PCOS, and genome-wide chronodisruption exists in ovarian GCs.

Circadian Rhythm and Concentration of Melatonin in Breast Cancer Patients.

BACKGROUND: Melatonin is a biomarker of the central circadian clock and its chronobiotic actions entraining circadian rhythms to the light-dark cycle are well known. Reduction in melatonin levels and altered circadian rhythms have been associated with a high risk of breast cancer. Melatonin has also been shown to display anti-proliferative effects on breast cancer growth and proliferation. Evaluation of melatonin circadian rhythm alterations in patients bearing breast cancer may have interesting prognostic and therapeutic applications. OBJECTIVE: To review studies evaluating the circadian rhythm of melatonin in breast cancer patients. The effects of surgery and chemotherapy on melatonin secretion were also reviewed. METHODS: Electronic databases, including PubMed/MEDLINE and Scopus, were searched from their inception to May 2020, using the keywords "Melatonin", "Circadian rhythm" and "Breast cancer". RESULTS: Patients with breast cancer maintain a circadian rhythm of melatonin secretion with relatively high levels during the night and low levels during the day, however, a reduction in nocturnal melatonin peak and decreased amplitude of melatonin circadian rhythms in these patients have also been reported. Melatonin levels can influence estrogen receptor concentrations in hormone-dependent estrogen- positive breast cancer. Chemotherapy alters melatonin levels and breast surgery tends to alter melatonin secretion at first-day post-operation. Melatonin levels correlate with clinical and psychological symptoms of breast cancer, such as sleep quality and depression severity. CONCLUSION: Circadian rhythm and the concentration of melatonin in the blood are altered in patients with breast cancers, and it can modify not only the sleep-wake cycle and, thus, patients' quality of life but due to melatonin's antioxidant effects, the effect of therapies can be modulated. Due to the heterogonous protocols used to assess melatonin and variable environmental factors during sampling, further studies need to control, such variables in order to tailor clinical trials based on melatonin rhythm adjustment and/or supplementation in breast cancer patients.

Melatonin exerts immunoregulatory effects by balancing peripheral effector and regulatory T helper cells in myasthenia gravis.

Myasthenia gravis (MG) is a prototypic organ-specific autoimmune disorder that, in most cases, is mainly mediated by antibodies against the acetylcholine receptor. Evidence implicates CD4+ T helper (Th) cells in the development of MG, whereas regulatory T cells (Tregs) are associated with disease resolution. Melatonin has important immunoregulatory effects in many T cell-mediated autoimmune diseases. However, there are few studies on the role of melatonin in MG. In the present study, we investigated serum melatonin levels and melatonin receptor expression in MG patients and healthy controls (HCs). We also evaluated the impact of melatonin administration on peripheral CD4+ Th cells and related cytokine production. Serum melatonin levels were lower in MG patients than in HCs, and MT1 expression was lower in PBMCs from MG patients than in those from HCs. Administration of melatonin significantly decreased Th1 and Th17 cell responses and proinflammatory cytokine production. Further investigation in vitro revealed that melatonin administration increased FoxP3 and IL-10 expression in CD4+ T cells from MG patients and enhanced the suppressive function of Tregs. These findings indicate that melatonin exerts immunoregulatory activity in MG by balancing effector and regulatory Th cell populations as well as by suppressing proinflammatory cytokine production.

Effects of a temperature rise on melatonin and thyroid hormones during smoltification of Atlantic salmon, Salmo salar.

Smoltification prepares juvenile Atlantic salmon (Salmo salar) for downstream migration. Dramatic changes characterize this crucial event in the salmon's life cycle, including increased gill Na+/K+-ATPase activity (NKA) and plasma hormone levels. The triggering of smoltification relies on photoperiod and is modulated by temperature. Both provide reliable information, to which fish have adapted for thousands of years, that allows deciphering daily and calendar time. Here we studied the impact of different photoperiod (natural, sustained winter solstice) and temperature (natural, ~ + 4° C) combinations, on gill NKA, plasma free triiodothyronine (T3) and thyroxine (T4), and melatonin (MEL; the time-keeping hormone), throughout smoltification. We also studied the impact of temperature history on pineal gland MEL production in vitro. The spring increase in gill NKA was less pronounced in smolts kept under sustained winter photoperiod and/or elevated temperature. Plasma thyroid hormone levels displayed day-night variations, which were affected by elevated temperature, either independently from photoperiod (decrease in T3 levels) or under natural photoperiod exclusively (increase in T4 nocturnal levels). Nocturnal MEL secretion was potentiated by the elevated temperature, which also altered the MEL profile under sustained winter photoperiod. Temperature also affected pineal MEL production in vitro, a response that depended on previous environmental acclimation of the organ. The results support the view that the salmon pineal is a photoperiod and temperature sensor, highlight the complexity of the interaction of these environmental factors on the endocrine system of S. salar, and indicate that climate change might compromise salmon's time "deciphering" during smoltification, downstream migration and seawater residence.

Melatonin Suppresses the Kainate Receptor-Mediated Excitation on Gonadotropin-Releasing Hormone Neurons in Female and Male Prepubertal Mice.

Melatonin, a pineal gland secretion, is an amphiphilic neurohormone involved in the biological and physiologic regulation of bodily functions. Numerous studies have shown the effects of melatonin on the release of gonadotropins and their actions at one or several levels of the hypothalamic-pituitary-gonadal axis. However, direct melatonin action on gonadotropin-releasing hormone (GnRH) neurons and its mechanism of action remain unclear. Here, plasma melatonin levels were measured and the effect of melatonin on GnRH neurons was assessed using brain slice patch clamp techniques. The plasma melatonin levels in prepubertal mice were higher than those in the adults. Melatonin itself did not change the firing activity of GnRH neurons. Interestingly, the kainate receptor-mediated responses but not the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)- and N-methyl-D-aspartic acid (NMDA)-induced responses were suppressed by melatonin in both the voltage clamp and current clamp modes. The inhibitory effects of the kainate-induced response by melatonin tended to increase with higher melatonin concentrations and persisted in the presence of tetrodotoxin, a voltage-sensitive Na+ channel blocker, or luzindole, a non-selective melatonin receptor antagonist. However, the response was completely abolished by pretreatment with pertussis toxin. These results suggest that melatonin can regulate GnRH neuronal activities in prepubertal mice by partially suppressing the excitatory signaling mediated by kainate receptors through pertussis toxin-sensitive G-protein-coupled receptors.

Sleep deprivation aggravated lipopolysaccharide/D-galactosamine-induced acute liver injury by suppressing melatonin production.

OBJECTIVE: Sleep loss is common in patients with liver injury, but the effects of sleep deprivation (SD) on liver injury remain unclear. In the present study, the potential effects of SD on acute liver injury and the underlying mechanisms have been investigated. METHODS: The sleep of male BALB/c mice has been deprived by using a modified multiple platform water bath for 3 days and acute liver injury was induced by intraperitoneal injection of lipopolysaccharide (LPS) and D-galactosamine (D-Gal). The degree of liver injury was detected by aminotransferase determination, histopathology and survival rate analysis. Inflammatory response and melatonin (MT) were measured by enzyme-linked immunosorbent assay (ELISA). In addition, hepatocyte apoptosis was determined by caspase activity measurement and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. RESULTS: We observed that SD increased plasma aminotransferases, TUNEL-positive hepatocytes, histological abnormalities and mortality rates in mice with LPS/D-Gal treatment. SD also promoted LPS/D-Gal-induced production of TNF-α and upregulated hepatic caspase-8, caspase-9, and caspase-3 activities in LPS/D-Gal-exposed mice. In addition, SD significantly decreased MT contents in plasma of mice with acute liver injury, but supplementation with MT reversed these SD-promoted changes. CONCLUSION: Our data suggested that SD exacerbated LPS/D-Gal-induced liver injury via decreasing melatonin production.

Altitude effect on sleep quality and serum melatonin levels in Chilean mining workers / Efecto de la Altitud en la calidad de sueño y niveles séricos de melatonina en trabajadores mineros en Chile

High altitude (HA) mining operations are a very important business in Chile, but reduced availability of oxygen affects the sleep quality, increasing the risk of accidents. An important regulator of sleep-wake cycle is the hormone Melatonin, produced by pineal gland as a sleep inductor. The aim of this study is to evaluate the effect of high altitude (4,500 m) on the quality of sleep of workers undergoing to Chronic Intermittent Hypobaric Hypoxia (CIHH) using self-reported surveys of sleepiness and sleep quality, measurement of sleep apnea (using nocturnal oximetry) and serum levels of melatonin. The Desaturation index (ID4) results revealed higher HA scores compared to sea level (SL). Regarding melatonin levels, the results show that it is increased in HA versus SL and this increase would be related to oxygen saturation during sleep. These data link sleep quality in HA to its melatonin levels, suggesting that melatonin may be a potential biomarker for sleep quality.

Interleukin-6 and Melatonin as Predictors of Cognitive, Emotional and Functional Ageing of Older People.

BACKGROUND: The ageing process causes a number of changes in the human immune and endocrine systems. The aim of this study was to assess the relationship between cognitive, emotional and functional skills as well lifestyle, versus selected biochemical indicators of the ageing process. METHODS: The cross-sectional study was conducted in a group of 121 people aged 60-90 residing in the Lesser Poland voivodship. The study used standardized research tools including the Barthel scale, Instrumental Activities of Daily Living (IADL) scale, Mini-Mental State Examination (MMSE), Life Orientation Test (LOT-R) and inventory of health behaviors (IHB). In addition, the concentration of IL-6 and melatonin in the blood plasma was determined. RESULTS: We determined the correlation between the level of IL-6 in a group of people over 75 years of age (requiring medical care), and results of the IADL scale. There was also a correlation between melatonin levels and the MMSE results in a group of people aged 60-75 who did not require constant medical care. CONCLUSIONS: IL-6 can be treated as a predictor of functional skills of people over 75 years of age, and melatonin can be perceived as a factor for recognizing cognitive impairment in elderly people who do not require constant medical assistance.