The Outcome of Photo-Therapy on Serum Calcium Values in Term Neonates: A Cross Sectional Study

Background: In the management of hyperbilirubinemia in neonates, phototherapy is an important treatment modality. Photo-therapy can cause skin rashes, diarrhoea, increase in body temperature, retinal damage and bronze baby syndrome. Photo-therapy is thought to influence serum calcium levels by inhibiting pineal melatonin secretion. Aims and Objectives: The aim of this research was to see how photo-therapy affected serum calcium values in a term neonate. Materials and Methods: Over the course of six months, 74 neonates were studied in the neonatology department of a tertiary healthcare centre in Central India. Results: Calcium values fell in 77 % of the neonates in our sample, but only one case fell into significant symptomatic hypocalcemic range (1 percent). Conclusion: According to the findings, neonates who are receiving photo-therapy have a higher risk of falling into the hypocalemic range. As a result, neonates should be strictly observed for calcium shifts and treated appropriately.

CircRNA-WNK2 acts as a ceRNA for miR-328a-3p to promote AANAT expression in the male rat pineal gland

Noncoding RNAs (ncRNAs), including miRNAs and circRNAs, which are expressed with a daily rhythm in the rat pineal gland, are associated with the regulation of melatonin secretion and other biological functions. However, the mechanisms of these molecules in the rat pineal gland are not yet fully understood. In this study, we found circR-WNK2 was highly expressed at night, which may be involved in the regulation of melatonin secretion through the ceRNA mechanism. By dual luciferase reporter, RNA pulldown, and FISH assays, we found that miR-328a-3p can target circR-WNK2 and the Aa-nat mRNA 3’UTR. Transfection experiments indicated that circR-WNK2 could competitively bind to miR-328a-3p, reduce miR-328a-3p expression, and promote Aa-nat gene expression and melatonin secretion. And by constructing an SCGx rat model, we found that ncRNAs expressed in the pineal gland was regulated by signals from the SCN. This finding supports the hypothesis that these noncoding RNAs may interact to shape the circadian rhythm through transcriptional processing in melatonin synthesis.

English MODULATION OF MELATONIN SECRETION WITH TRANSCUTANEOUS AURICULAR NERVE STIMULATION: A CASE STUDY

The main study objective was to test the hypothesis that selective electrical transcutaneous auricular nerve stimulation (tANS) under forenoon daylight conditions induces melatonin secretion in a 64-year-old male patient with angina pectoris, hypercholesterolomy and coronary artery disease, assuming that it has beneficial effects on accompanied insomnia (Regensburg Insomnia Scale (RIS) = 22 points, the total score ranges from 0 to 40). Silicone stimulation plugs, with two platinum stimulating cathodes each, were inserted into the left and right external ears. Afterwards, one-second-long pulse trains of cathodic, biphasic and current regulated stimulating pulses at stimulating charge density Cd of 50.88 µC/cm2 and frequency of 25 Hz, were delivered for 30 min to selected sites at the upper and lower part of the left and right Cymba Conchae (CC), respectively. The common anode was attached to the neck. The time gap between the pulse trains was measured by the patient using a tactile sensor and was about 250 ms. The results showed that selective tANS under forenoon daylight conditions increased melatonin saliva levels in all the trials accomplished in a patient. Precisely, the lowest increase was obtained in trials with lower right (LR) CC, while the highest increase was obtained in upper-right (UR) CC trials.

Preliminary Study on Changes of Sleep EEG Power and Plasma Melatonin in Male Patients With Major Depressive Disorder After 8 Weeks Treatment

Objective: To clarify the effects of escitalopram on sleep EEG power in patients with Major depressive disorder (MDD).Method: Polysomnography (PSG) was detected overnight, and blood samples were collected at 4 h intervals over 24 h from 13 male healthy controls and 13 male MDD patients before and after treatment with escitalopram for 8 weeks. The outcome measures included plasma melatonin levels, sleep architecture, and the sleep EEG power ratio.Results: Compared with healthy controls, MDD patients presented abnormalities in the diurnal rhythm of melatonin secretion, including peak phase delayed 3 h and a decrease in plasma melatonin levels at night and an increase at daytime, accompanied by sleep disturbances, a decrease in low-frequency bands and an increase in high-frequency bands, and the dominant right-side brain activity. Several of these abnormalities (abnormalities in the diurnal rhythm of melatonin secretion, partial sleep architecture parameters) persisted for at least the 8-week testing period.Conclusions: Eight weeks of treatment with escitalopram significantly improved subjective sleep perception and depressive symptoms of patients with MDD, and partially improved objective sleep parameters, while the improvement of circadian rhythm of melatonin was limited.

Serotonin modulates melatonin synthesis as an autocrine neurotransmitter in the pineal gland

The pineal gland secretes melatonin principally at night. Regulated by norepinephrine released from sympathetic nerve terminals, adrenergic receptors on pinealocytes activate aralkylamine N-acetyltransferase that converts 5-hydroxytryptamine (5-HT, serotonin) to N-acetylserotonin, the precursor of melatonin. Previous studies from our group and others reveal significant constitutive secretion of 5-HT from pinealocytes. Here, using mass spectrometry, we demonstrated that the 5-HT is secreted primarily via a decynium-22–sensitive equilibrative plasma membrane monoamine transporter instead of by typical exocytotic quantal secretion. Activation of the endogenous 5-HT receptors on pinealocytes evoked an intracellular Ca2+ rise that was blocked by RS-102221, an antagonist of 5-HT2C receptors. Applied 5-HT did not evoke melatonin secretion by itself, but it did potentiate melatonin secretion evoked by submaximal norepinephrine. In addition, RS-102221 reduced the norepinephrine-induced melatonin secretion in strips of pineal gland, even when no exogenous 5-HT was added, suggesting that the 5-HT that is constitutively released from pinealocytes accumulates enough in the tissue to act as an autocrine feedback signal sensitizing melatonin release.

Testis development in the Japanese eel is affected by photic signals through melatonin secretion

Objective According to reported spawning characteristics of Japanese eel, Anguilla japonica, which exhibit spawning and migration patterns that are synchronized with lunar cycles and photoperiod, we hypothesized that a close association exists between specific photic signals (daylight, daylength, and moonlight) and endocrinological regulation. Given the photic control in melatonin secretion, this hypothesis was tested by investigating whether melatonin signals act as mediators relaying photic signals during testis development in the eel. Methods We examined changes in melatonin-secretion patterns using time-resolved fluorescence immunoassays in sexually immature and mature male Japanese eels under the condition of a new moon (NM) and a full moon (FM). Results The eye and plasma melatonin levels exhibited a nocturnal pattern under a 12-h light: dark cycle (12L12D) or under constant darkness (DD), but not with constant light (LL). Eye melatonin levels were similar under the 12L12D and short-day (9L15D) conditions. In the long-day condition (15L9D), secreted plasma melatonin levels were stable, whereas short-day melatonin secretion began when darkness commenced. Sexual maturation began at 8 weeks following intraperitoneal injection of human chorionic gonadotropin (hCG), and NM exposure led to significantly higher eye and plasma melatonin levels compared with those detected under FM exposure.

O031 Nocturnal melatonin secretion in post-treatment breast cancer patients: a preliminary study

Purpose Breast-cancer patients frequently report of poor sleep-quality. Although the pathophysiology is unclear, circadian-sleep misalignment is a plausible mechanism. We compared nocturnal melatonin-secretion, a circadian rhythm marker, in post-menopausal, post-treatment (≥12-months) female breast-cancer patients (BCG), with post-menopausal female controls with no history of cancer (CG) Methods We recruited 6 BCG and 10 CG from Westmead Hospital breast-cancer outpatient clinic or hospital-staff community, respectively. Participants completed the Pittsburgh Sleep Quality Index (PSQI; >5 PSQI-score=poor sleep-quality) and ~7 days of home-actigraphy (Philips Actiwatch-2, Philips Respironics, USA) to ascertain habitual bed-time (HBT). Later, participants completed an overnight, in-laboratory study, with saliva sampled (n=13) at regular intervals under strict dim-light conditions (<1 lux). Salivary-melatonin concentrations were quantified via radioimmunoassay (University of Adelaide). We measured 1) clock-time when salivary-melatonin concentrations reached 4pg/mL (melatonin onset-[DLMO-4pg/ml]) and 2) time-interval between HBT and DLMO-4pg/ml (indicates circadian-sleep misalignment-[PAR-DLMO]). Data were expressed as median [interquartile range], and compared using 2-sided Mann Whitney U-tests. p<0.05 was considered significant. Results BCG and CG had similar ages (62.5 [59.5–67.3] vs. 58.5 [54.0–66.3] yrs, respectively; p=0.23). Compared with CG, BCG had higher PSQI-scores (8.50 [5.25–10.75] vs. 4.00 [3.75–5.50] a.u.; p=0.07), but similar HBT (22:49 [21:46-23:38] vs. 22:17 [21:59-22:21] h:min; p=0.26). BCG had later DLMO-4pg/ml (20:46 [20:01-22:03] vs. 18:23 [17:55-20:07] h:min; p=0.03) and shorter PAR-DLMO (1.43 [0.96–2.38] vs. 3.63 [2.18–3.90] hrs; p=0.09), than CG. Conclusion Preliminary data indicate BCG had poorer sleep-quality, delayed melatonin onset, and altered circadian-sleep alignment; compared with CG. We speculate disrupted nocturnal melatonin-secretion potentially influences poor sleep-quality reported by breast-cancer patients.

Negative regulation of melatonin secretion by melatonin receptors in ovine pinealocytes

Melatonin (MLT) is a biological modulator of circadian and seasonal rhythms and reproduction. The photoperiodic information is detected by retinal photoreceptors and transmitted through nerve transmissions to the pineal gland, where MLT is synthesized and secreted at night into the blood. MLT interacts with two G protein-coupled receptors, MT1 and MT2. The aim of our work was to provide evidence for the presence of MLT receptors in the ovine pineal gland and define their involvement on melatonin secretion. For the first time, we identified the expression of MLT receptors with the specific 2-[125I]-MLT agonistic radioligand in ovin pinealocytes. The values of Kd and Bmax are 2.24 ± 1.1 nM and 20 ± 6.8 fmol/mg. MLT receptors are functional and inhibit cAMP production and activate ERK1/2 through pertussis toxin-sensitive Gi/o proteins. The MLT receptor antagonist/ inverse agonist luzindole increased cAMP production (189 ± 30%) and MLT secretion (866 ± 13%). The effect of luzindole on MLT secretion was additive with the effect of well-described activators of this pathway such as the β-adrenergic agonist isoproterenol and the α-adrenergic agonist phenylephrine. Co-incubation of all three compounds increased MLT secretion by 1236 ± 199%. These results suggest that MLT receptors are involved in the negative regulation of the synthesis of its own ligand in pinealocytes. While adrenergic receptors promote MLT secretion, MLT receptors mitigate this effect to limit the quantity of MLT secreted by the pineal gland.

A Genome-Wide Association Study for Melatonin Secretion

SummaryPurpose: Melatonin exerts a wide range of effects among various tissues and organs. However, there is currently no study to investigate the genetic determinants of melatonin secretion. Here, we conducted a genome-wide association study (GWAS) for melatonin secretion using morning urine 6-hydroxymelatonin sulfate-to-creatinine ratio (UMCR). Methods: We initially enrolled 5,000 participants from Taiwan Biobank in this study. After excluding individuals that did not have their urine collected in the morning and those who failed to pass quality control, association of single nucleotide polymorphisms with log-transformed UMCR adjusted for age, sex and principal components of ancestry were analyzed. A second model additionally adjusted for estimated glomerular filtration rate (eGFR). Results: A total of 2,504 participants underwent the genome-wide analysis. Six candidate loci associated with log UMCR (P value ranging from 7.54 x 10-7 to 4.65 x 10-6) encompassing GALNT15, ZFHX3, NKAIN2, MME and NBPF22P were identified. Similar results were yielded with further adjustment for eGFR. Interestingly, the identified genes are associated with central nervous system function and clinical condition such as Alzheimer's disease or sleep disorders.Conclusions: We conducted the first GWAS for melatonin secretion and identified six candidate genetic loci associated with melatonin level. Replication and functional studies are needed in the future.