Journal of Pineal Research最新文献

Circadian rhythm disruption (CRD), stemming from sleep disorders and/or shift work, is a risk factor for reproductive dysfunction. CRD has been reported to disturb nocturnal melatonin signaling, which plays a crucial role in female reproduction as a circadian regulator and an antioxidant. The hypothalamic-pituitary-ovarian (HPO) axis regulates female reproduction, with luteinizing hormone (LH) pulse pattern playing a pivotal role in folliculogenesis and steroidogenesis. However, the effect of CRD on the HPO axis and the involvement of melatonin remains unclear. Female CBA/CaJ mice underwent CRD modeling, which involves alternating between standard light conditions and an 8-h advance schedule every 3 days for 8 weeks, whereas control mice were maintained under a standard 12:12-h light/dark (LD) cycle. Subsequent measurements of diurnal melatonin levels, LH pulse patterns assessments via serial tail-tip blood sampling and evaluations of ovarian function were conducted. CRD altered the circadian rhythms of wheel-running activity and melatonin secretion in mice and led to an augmented LH pulse pattern, evidenced by increased LH pulse frequency, mean LH levels, and pituitary LH beta-subunit (LHβ) expression, irregular estrous cycles, abnormal luteal function, altered endocrine function, and ovarian oxidative stress. Melatonin treatment (10 mg/kg/day for 4 weeks) significantly improved the HPO axis disorder in CRD mice, decreasing the enhanced LH pulse frequency and pituitary LHβ expression. These findings were further validated using an in vitro LβT2 cell perfusion model. Furthermore, melatonin restored ovarian function and scavenged reactive oxygen species, thereby preventing apoptosis and preserving ovarian function. This study offers new insights into the impact of CRD on the HPO axis and emphasizes the potential of melatonin supplementation in mitigating its effects on female reproduction.

Light environment in the Arctic differs widely with the seasons. Studies of relationships between objectively measured circadian phase and amplitude of light exposure and melatonin in community-dwelling Arctic residents are lacking. This investigation combines cross-sectional (n = 24–62) and longitudinal (n = 13–27) data from week-long actigraphy (with light sensor), 24-h salivary melatonin profiles, and proxies of metabolic health. Data were collected within the same week bracketing spring equinox (SE), and winter/summer solstices (WS/SS). Drastic seasonal differences in blue light exposure (BLE) corresponded to seasonal changes in the 24-h pattern of melatonin, which was phase delayed and reduced in normalized amplitude (NA) during WS/SS compared to SE. The extent of individual melatonin's acrophase and Dim Light Melatonin Onset (DLMO) change from SE to WS correlated with that from SE to SS. Although similar in extent and direction, melatonin phase changes versus SE were linked to morning BLE deficit in WS, contrasting to evening BLE excess in SS. Seasonal changes in sleep characteristics were closely associated with changes in the phases of BLE and melatonin. Proxies of metabolic health included triglycerides (TG), high-density lipoprotein cholesterol (HDL), TG/HDL ratio, and cortisol. Adverse seasonal changes in these proxies were associated with delayed acrophases of BLE and melatonin during WS and SS. TG and TG/HDL were higher in WS and SS than in SE, and cross-sectionally correlated with later melatonin and BLE acrophases, while lower HDL was associated with later BLE onset and later melatonin acrophase. Overall, this study shows that optimal 24-h patterns of light exposure during SE is associated with an earlier acrophase and a larger 24-h amplitude of melatonin, and that both features are linked to better metabolic health. Improving light hygiene, in particular correcting winter morning light deficit and summer evening light excess may help maintain metabolic health at high latitudes. Novel solutions for introducing proper circadian light hygiene such as human-centric light technologies should be investigated to address these issues in future studies.

The dried root of Peucedanum praeruptorum is often used medicinally and has high pyran- and furanocoumarin content. Although exogenous melatonin (MT) impacts the regulation of plant growth, stress responses, secondary metabolism, etc., it remains unclear whether MT regulates the vegetative growth and development of P. praeruptorum. Thus, the aim of the current study is to characterize the effects of different exogenous MT concentrations on the physiological functions, photosynthesis, antioxidant systems, hormone induction, and coumarin synthesis of P. praeruptorum. Different MT concentrations exert distinct regulatory effects on P. praeruptorum growth and the expression of genes related to coumarin synthesis. Treatment of P. praeruptorum with low concentrations of MT increases photosynthesis and leaf growth compared to the control, while high concentrations reduce root vitality and elongation and decrease the expression of photosynthetic system genes. Low concentrations of MT also significantly increase antioxidant enzyme activity and photosynthetic pigment content and modulate the levels of IAA, gibberellic acid, salicylic acid, jasmonic acid, abscisic acid, and endogenous MT. Moreover, MT increases the activity of the MT synthesis enzymes tryptophan decarboxylase, tryptophan hydroxylase, tryptamine-5-hydroxylase, serotonin N-acetyltransferase, acetylserotonin O-methyltransferase, and caffeic acid O-methyltransferase, and promotes the accumulation of isoscopoletin, scopoletin, peucedanocoumarin II, praeruptorin A, praeruptorin B, and praeruptorin E. MT also upregulates most genes associated with coumarin synthesis, including PAL1, C4H, 4CL-3, C3H-1, F6H-1, CCoAMT, OMT-1, CYP71AJ1, CYP84A1-1, S8H-1, PT-1, and COSY-1. These findings demonstrate that MT may improve P. praeruptorum growth and development while promoting the synthesis of coumarin components.

Melatonin has multiple proposed therapeutic benefits including antioxidant properties, circadian rhythm synchronisation and sleep promotion. Since these areas are also recognised risk factors for dementia, melatonin has been hypothesised to slow cognitive decline in older adults.

Participants with Mild Cognitive Impairment (MCI) were recruited from the community for a 12-week randomised placebo-controlled parallel, feasibility trial of 25 mg oral melatonin nightly. Primary outcomes were feasibility, acceptability, and tolerability. Secondary efficacy outcomes were brain oxidative stress, cognition, mood, and sleep at 12 weeks.

Forty participants (mean [SD] age = 68.2 [4.7] years; 19 female) were randomised. Feasibility, defined as those who met eligibility criteria, was 42/389, 11%. Acceptability, determined by the proportion of eligible people who agreed to be randomised, was 40/44, 91%. Tolerability, determined by adherence to the nightly melatonin and completion of the main secondary outcome (Magnetic Resonance Spectroscopy scan) was over the pre-defined 80% threshold for all participants. The study was not powered to detect effectiveness. Accordingly, there were no significant differences between melatonin and placebo interventions in any of the secondary outcomes.

The protocol was developed, and successfully implemented, with the planned number of eligible participants recruited. All participants were able to complete all aspects of the trial, including online visits and assessments, with no differences in adverse events between groups. This is promising for future trials, which should conduct the study with a larger sample size and longer duration to yield necessary efficacy data.