Journal of Pineal Research最新文献

{"title":"Melatonin, an Antitumor Necrosis Factor Therapy.","authors":"Ana Isabel Álvarez-López, Ivan Cruz-Chamorro, Patricia Judith Lardone, Ignacio Bejarano, Karla Aspiazu-Hinostroza, Eduardo Ponce-España, Guillermo Santos-Sánchez, Nuria Álvarez-Sánchez, Antonio Carrillo-Vico","doi":"10.1111/jpi.70025","DOIUrl":"10.1111/jpi.70025","url":null,"abstract":"<p><p>Tumor necrosis factor (TNF) is a biomarker of inflammation whose levels are elevated in patients with several diseases associated with dysregulation of the immune response. The main limitations of currently used anti-TNF therapies are the induction of immunodepression, which in many cases leads to serious adverse effects such as infection and cancer, and the inability to cross the blood-brain barrier in neuroinflammatory conditions. Melatonin, in addition to being a chronobiotic compound, is widely known for its antioxidant and immunomodulatory capacity to control inflammatory processes in different pathological contexts. The aim of the present review is to address human-based studies that describe the effect of melatonin on TNF production. The review includes all the articles published in PubMed databases until April 15, 2024. After depuration, 45 studies were finally included in the review, 23 related to the in vitro action of melatonin in human cells and 22 in vivo studies in humans. Most of the data reviewed support the idea that melatonin has an immunosuppressive effect on TNF levels, which, together with its low toxicity profile, low cost, and ability to cross the blood-brain barrier, points to melatonin as a potential anti-TNF therapy. Therefore, improving our knowledge of the action of melatonin in regulating TNF through appropriate clinical trials would reveal the true potential of this molecule as a possible anti-TNF therapy.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":"e70025"},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11685806/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142908736","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Relating Photoperiod and Outdoor Temperature With Sleep Architecture in Patients With Neuropsychiatric Sleep Disorders.","authors":"Katy Sarah Weihrich, Frederik Bes, Jan de Zeeuw, Martin Haberecht, Dieter Kunz","doi":"10.1111/jpi.70030","DOIUrl":"https://doi.org/10.1111/jpi.70030","url":null,"abstract":"<p><p>While artificial light in urban environments was previously thought to override seasonality in humans, recent studies have challenged this assumption. We aimed to explore the relationship between seasonally varying environmental factors and changes in sleep architecture in patients with neuropsychiatric sleep disorders by comparing two consecutive years. In 770 patients, three-night polysomnography was performed at the Clinic for Sleep & Chronomedicine (St. Hedwig Hospital, Berlin, Germany) in 2018/2019. Sleep times were adjusted to patients' preferred schedules, patients slept in, and were unaware of day-night indicators. Digital devices and clocks were not allowed. Days were spent outside the lab with work or naps not allowed. After exclusions (mostly due to psychotropic medication), analysis was conducted on the second PSG-night in 377 patients (49.1 ± 16.8 year; 54% female). Sleep parameters were plotted as 90-day moving-averages (MvA) across date-of-record. Periodicity and seasonal windows in the MvA were identified by utilizing autocorrelations. Linear mixed-effect models were applied to seasonal windows. Sleep parameters were correlated with same-day photoperiod, temperature, and sunshine duration. The MvA of total sleep time (TST) and REM sleep began a 5-month-long decline shortly after the last occurrence of freezing 24-h mean temperatures (correlation of TST between 2018 and 2019 at 2-month lag: rs₃₆₁ = 0.87, p < 0.001; maximum peak-to-nadir amplitude: ΔTST ~ 62 min, ΔREM ~ 24 min). The MvA nadirs of slow wave sleep (SWS) occurred approximately at the autumnal equinox (correlation between 2018 and 2019: rs₃₆₁ = 0.83, p < 0.001). Post hoc testing following significant linear mixed-effect model indicate that TST and REM sleep were longer around November till February than May till August (ΔTST = 36 min; ΔREM = 14 min), while SWS was 23 min longer around February till May than August till November. Proportional seasonal variation of SWS and of REM sleep as percentages of TST differed profoundly (SWS = 31.6%; REM = 8.4%). In patients with neuropsychiatric sleep disorders living in an urban environment, data collected in 2018 show similar patterns and magnitudes in seasonal variation of sleep architecture as the 2019 data. Interestingly, whereas SWS patterns were consistent between years with possible links to photoperiod, annual variations of TST and REM sleep seem to be related to times of outside freezing temperature. For generalization, the data need to be confirmed in a healthy population. No clinical trial was registered.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":"e70030"},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11707406/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142941978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Protective Effects of Melatonin on Kidney Function Against Contrast Media-Induced Kidney Damage in Patients With Chronic Kidney Disease: A Prospective, Randomized, Double-Blinded, Placebo-Controlled Trial.","authors":"Prit Kusirisin, Nattayaporn Apaijai, Kajohnsak Noppakun, Srun Kuanprasert, Siriporn C Chattipakorn, Nipon Chattipakorn","doi":"10.1111/jpi.70031","DOIUrl":"https://doi.org/10.1111/jpi.70031","url":null,"abstract":"<p><p>Patients with chronic kidney disease (CKD) are at increased risk of acute kidney injury following exposure to contrast media. We evaluated the effect of melatonin, a potent antioxidant, as a protective strategy against contrast-induced acute kidney injury (CI-AKI), with a focus on molecular mechanisms. We randomized patients with an eGFR < 60 mL/min/1.73 m² undergoing coronary angiography (CAG) into melatonin (10 mg twice daily) or placebo groups. Treatment started 48 h before CAG and continued for a total of 6 days. Peripheral blood mononuclear cells (PBMCs) were collected at baseline, at the time of CAG, and at 6, 24, 48, 72 h, and Day 30 post-procedure. The primary outcome was the incidence of CI-AKI; secondary outcomes included kidney function, oxidative stress, mitochondrial function, and cell death pathways. Forty patients were randomized into either the treatment or placebo group. All subsequent analyses were conducted on an as-treat basis. The incidence of CI-AKI was significantly lower in the melatonin group compared to the placebo group (25% vs. 60%, p = 0.025). The melatonin group showed a significantly smaller percentage change in plasma neutrophil gelatinase-associated lipocalin (NGAL) at all time points. In the PBMC study, cellular oxidative stress was significantly reduced in the melatonin group at each time point, and mitochondrial oxidative stress was lower at 48-72 h. Mitochondrial respiration improved significantly, and both necrosis and necroptosis were reduced at 24 h. Melatonin administration effectively reduced the incidence of CI-AKI in CKD patients undergoing CAG. This protective effect was associated with decreased oxidative stress, enhanced mitochondrial function, and reduced cell death, suggesting melatonin as a promising preventive strategy for CI-AKI. Trial Registration: TCTR20210123004.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":"e70031"},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997050","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Resetting of the Human Circadian Melatonin Rhythm by Ambient Hypoxia.","authors":"Titiaan E Post, Riccardo De Gioannis, Jan Schmitz, Martin Wittkowski, Tina Martin Schäper, Anna Wrobeln, Joachim Fandrey, Marie-Therese Schmitz, Joseph S Takahashi, Jens Jordan, Eva-Maria Elmenhorst, Daniel Aeschbach","doi":"10.1111/jpi.70029","DOIUrl":"https://doi.org/10.1111/jpi.70029","url":null,"abstract":"<p><p>Circadian clocks in the body drive daily cycles in physiology and behavior. A master clock in the brain maintains synchrony with the environmental day-night cycle and uses internal signals to keep clocks in other tissues aligned. Work in cell cultures uncovered cyclic changes in tissue oxygenation that may serve to reset and synchronize circadian clocks. Here we show in healthy humans, following a randomized controlled single-blind counterbalanced crossover study design, that one-time exposure to moderate ambient hypoxia (FiO₂ ~15%, normobaric) for ~6.5 h during the early night advances the dim-light onset of melatonin secretion by 9 min (95% CI: 1-16 min). Exposure to moderate hypoxia may thus be strong enough to entrain circadian clocks to a 24-h cycle in the absence of other entraining cues. Together, the results provide direct evidence for an interaction between the body's hypoxia-sensing pathway and circadian clocks. The finding offers a mechanism through which behaviors that change tissue oxygenation (e.g., exercise and fasting/eating) can affect circadian timing and through which hypoxia-related diseases (e.g., obstructive sleep apnea and chronic obstructive pulmonary disease) can result in circadian misalignment and associated pathologies. Trial Registration: Registration number: DRKS00023387; German Clinical Trials Register: http://www.drks.de.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":"e70029"},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11740168/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142997053","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Melatonin Alleviates Circadian Rhythm Disruption-Induced Enhanced Luteinizing Hormone Pulse Frequency and Ovarian Dysfunction.","authors":"Yujing Li, Tianjiao Pei, Huili Zhu, Ruiying Wang, Lukanxuan Wu, Xin Huang, Fangyuan Li, Xinyu Qiao, Yuchan Zhong, Wei Huang","doi":"10.1111/jpi.70026","DOIUrl":"https://doi.org/10.1111/jpi.70026","url":null,"abstract":"<p><p>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.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":"e70026"},"PeriodicalIF":8.3,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142930127","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"3-Month Melatonin Supplementation to Reduce Brain Oxidative Stress and Improve Sleep in Mild Cognitive Impairment: A Randomised Controlled Feasibility Trial","authors":"Zoe Menczel Schrire,&nbsp;Craig L. Phillips,&nbsp;Shantel L. Duffy,&nbsp;Nathaniel S. Marshall,&nbsp;Loren Mowszowski,&nbsp;Haley M. La Monica,&nbsp;Lachlan Stranks,&nbsp;Christopher J. Gordon,&nbsp;Julia L. Chapman,&nbsp;Bandana Saini,&nbsp;Sharon L. Naismith,&nbsp;Ronald R. Grunstein,&nbsp;Camilla M. Hoyos","doi":"10.1111/jpi.70019","DOIUrl":"10.1111/jpi.70019","url":null,"abstract":"<div>\u0000 \u0000 <p>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.</p>\u0000 <p>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.</p>\u0000 <p>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.</p>\u0000 <p>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.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142862704","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Skeletal Phenotyping of Period-1-Deficient Melatonin-Proficient Mice","authors":"Olaf Bahlmann,&nbsp;Shahed Taheri,&nbsp;Manuela Spaeth,&nbsp;Katrin Schröder,&nbsp;Arndt F. Schilling,&nbsp;Christian Dullin,&nbsp;Erik Maronde","doi":"10.1111/jpi.70020","DOIUrl":"10.1111/jpi.70020","url":null,"abstract":"<p>In mice, variability in adult bone size and density has been observed among common inbred strains. Also, in the group of genes regulating circadian rhythmicity in mice, so called clock genes, changes in body size and skeletal parameters have been noted in knockout mice. Here, we studied the size and density of prominent bones of the axial and appendicular skeleton of clock gene <i>Period</i>-1-deficient (<i>Per</i>1^-/-) mice by means of microcomputed tomography. Our data show shorter spinal length, smaller and less dense femora and tibiae, but no significant changes in the shape of the skull and the length of the head. Together with the significantly lower total body weight of <i>Per</i>1^-/- mice, we conclude that <i>Per</i>1-deficiency in a melatonin-proficient mouse strain is associated with an altered body phenotype with smaller appendicular (hind limb) bone size, shorter spine length and lower total body weight while normal head length and brain weight. The observed changes suggest an involvement of secondary bone mineralisation with impact on long bones, but lesser impact on those of the skull. Evidence and overall physiological implications of these findings are discussed.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70020","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142851620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Identification of Predictors of Shift Work Adaptation and Its Association With Immune, Hormonal and Metabolite Biomarkers","authors":"Barbara N. Harding,&nbsp;Ana Espinosa,&nbsp;Gemma Castaño-Vinyals,&nbsp;Oscar J. Pozo,&nbsp;Debra J. Skene,&nbsp;Mariona Bustamante,&nbsp;Maria Mata,&nbsp;Ruth Aguilar,&nbsp;Carlota Dobaño,&nbsp;Valentin Wucher,&nbsp;José Maria Navarrete,&nbsp;Patricia Such Faro,&nbsp;Antonio Torrejón,&nbsp;Manolis Kogevinas,&nbsp;Kyriaki Papantoniou","doi":"10.1111/jpi.70017","DOIUrl":"10.1111/jpi.70017","url":null,"abstract":"<p>We explored predictors of shift work adaptation and how it relates to disease risk biomarker levels. These analyses included 38 male, rotating shift workers, sampled twice at the end of a 3-week night shift and a 3-week day shift rotation. Participants collected all 24-h urine voids, wore activity sensors, and responded to questionnaires during each shift. Using cosinor analysis, we derived the main period of urinary 6-sulfatoxymelatonin (aMT6s) production. Adaptation was defined as the overlap between the main aMT6s production period and sleep period assessed with actigraphy. We used linear models to identify predictors of adaptation to each shift and assessed associations between adaptation profiles and hormone, cytokine, and metabolite biomarker levels. The median duration of overlap (adaptation) was 3.85 h (IQR 2.59–5.03) in the night and 2.98 (IQR 2.17–4.11) in the day shift. In the night shift, a later chronotype (coeff: −1.16, 95% CI −1.87, −0.45) and increased light at night (coeff: −0.97, 95% CI −1.76, −0.18) were associated with poorer adaptation, while longer sleep duration was associated with better adaptation (coeff: 0.46, 95% CI 0.04, 0.88). In the day shift, later sleep onset was associated with worse adaptation (coeff: −0.06, 95% CI −0.12, −0.01), while longer sleep duration was associated with better adaptation (coeff: 0.54, 0.26, 0.81). Results suggest higher androgen and inflammatory marker levels and lower levels of several metabolite markers among less adapted individuals. Chronotype, sleep, and light at night were all associated with night or day shift adaptation. Given the small sample size, results should be viewed as exploratory, but may inform interventions to optimize adaptation of rotating shift workers.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70017","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142833321","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Activation of the Melatonin Receptor MT1 by the Natural Product Gastrodin to Promote Sleep","authors":"Lijing Zhang,&nbsp;Mengli Lan,&nbsp;Hui Chen,&nbsp;Richard Ward,&nbsp;Ya Zhao,&nbsp;Jing Guo,&nbsp;Lang Xiong,&nbsp;Xiuyu Yang,&nbsp;Yuxuan Pu,&nbsp;Cheng Xiang,&nbsp;Su An,&nbsp;Xiaoxi Guo,&nbsp;Tian-Rui Xu,&nbsp;Yang Yang","doi":"10.1111/jpi.70016","DOIUrl":"10.1111/jpi.70016","url":null,"abstract":"<div>\u0000 \u0000 <p>The activation of melatonin receptors, belonging to the G-protein coupled receptors (GPCRs) superfamily, has been recognized as a vital approach in the clinical management of sleep disorders. Although the natural agonist melatonin and synthetic agonists (e.g., ramelteon) targeting these receptors have been extensively studied, the identification of natural compounds acting as ligands remains elusive. We applied a combination of methods including GPCR-induced ERK1/2 MAP kinase phosphorylation assay, inhibition of forskolin-stimulated cAMP production, drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), solvent-induced protein precipitation (SIP), 2-[¹²⁵I]-iodomelatonin binding assay, fluorescence resonance energy transfer (FRET), and molecular docking to investigate MT₁ activation by gastrodin and the gastrodin–MT₁ interaction. The in vivo study was performed with mice whose MT₁ receptors were knocked down in the suprachiasmatic nucleus (SCN) of the brain. The sleep behavior and sleep-related hypothalamic neurotransmitters were evaluated. The results identified that the gastrodin acted as an agonist of MT₁ through direct binding to the receptor. The interaction of gastrodin-MT₁ was similar to that of melatonin–MT₁. The in vivo sleep-promoting effect of the gastrodin depended on the presence of MT₁ in the SCN and was associated with the hypothalamic neurotransmitters, similarly to melatonin.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816759","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sex-Specific Metabolic Effects of Gestational Chronodisruption and Maternal Melatonin Supplementation in Rat Offspring","authors":"Natalia Méndez,&nbsp;Fernando Corvalan,&nbsp;Diego Halabi,&nbsp;Abigail Vasquez,&nbsp;Karina Vergara,&nbsp;Hector Noriega,&nbsp;Pamela Ehrenfeld,&nbsp;Katiushka Sanhueza,&nbsp;Maria Seron-Ferre,&nbsp;Guillermo J. Valenzuela,&nbsp;Claudia Torres-Farfan","doi":"10.1111/jpi.70015","DOIUrl":"10.1111/jpi.70015","url":null,"abstract":"<div>\u0000 \u0000 <p>Gestational chronodisruption, increasingly common due to irregular light exposure, disrupts maternal-fetal circadian signaling, leading to long-term health issues in offspring. We utilized a chronic photoperiod shifting model (CPS) in pregnant rats to induce chronodisruption and investigated the potential mitigating effects of maternal melatonin supplementation (CPS + Mel). Male and female offspring were evaluated at 3 ages (90, 200, and 400 days of age) for metabolic profiles, hormonal responses, cytokine levels, and adipose tissue activity. Our findings indicate that gestational chronodisruption leads to increased birth weight by approximately 15% in male and female offspring and increased obesity prevalence in male offspring, accompanied by a 30% reduction in nocturnal melatonin levels and a significant disruption in corticosterone rhythms. Male CPS offspring also exhibited decreased lipolytic activity in white adipose tissue, with a 25% reduction in glycerol release compared to controls, indicating impaired metabolic flexibility. In contrast, female offspring, while less affected metabolically, showed a 25% increase in adipose tissue lipolytic activity and higher levels of pro-inflammatory cytokines such as IL-6 (increased by 40%). Scheduled melatonin supplementation in chronodisrupted mothers, administered throughout gestation, effectively normalized birth weights in both sexes, reduced obesity prevalence in males by 18%, and improved lipolytic activity in male offspring, bringing it closer to control levels. In females, melatonin supplementation moderated cytokine levels, reducing IL-6 by 35% and restoring IL-10 levels to near-control values. These results highlight the importance of sex-specific prenatal interventions, particularly the role of melatonin in preventing disruptions to fetal metabolic and inflammatory pathways caused by gestational chronodisruption. Melatonin treatment would prevent maternal circadian rhythm misalignment, thereby supporting healthy fetal development. This study opens new avenues for developing targeted prenatal care strategies that align maternal and fetal circadian rhythms, mitigating the long-term health risks associated with chronodisruption during pregnancy.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142793946","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}