Journal of Pineal Research最新文献

{"title":"Light Environment of Arctic Solstices is Coupled With Melatonin Phase-Amplitude Changes and Decline of Metabolic Health","authors":"Denis Gubin,&nbsp;Konstantin Danilenko,&nbsp;Oliver Stefani,&nbsp;Sergey Kolomeichuk,&nbsp;Alexander Markov,&nbsp;Ivan Petrov,&nbsp;Kirill Voronin,&nbsp;Marina Mezhakova,&nbsp;Mikhail Borisenkov,&nbsp;Aislu Shigabaeva,&nbsp;Natalya Yuzhakova,&nbsp;Svetlana Lobkina,&nbsp;Julianna Petrova,&nbsp;Olga Malyugina,&nbsp;Dietmar Weinert,&nbsp;Germaine Cornelissen","doi":"10.1111/jpi.70023","DOIUrl":"10.1111/jpi.70023","url":null,"abstract":"<div>\u0000 \u0000 <p>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 (<i>n</i> = 24–62) and longitudinal (<i>n</i> = 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.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"77 1","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891086","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":"Correction to “The Role of MEK1/2 and MEK5 in Melatonin-Mediated Actions on Osteoblastogenesis, Osteoclastogenesis, Bone Microarchitecture, Biomechanics, and Bone Formation”","authors":"","doi":"10.1111/jpi.70024","DOIUrl":"10.1111/jpi.70024","url":null,"abstract":"<p>F. Munmun, O. A. Mohiuddin, V. T. Hoang, et al., “The Role of MEK1/2 and MEK5 in Melatonin-Mediated Actions on Osteoblastogenesis, Osteoclastogenesis, Bone Microarchitecture, Biomechanics, and Bone Formation,” <i>Journal</i> of <i>Pineal Research</i> 73 (2022): e12814, https://doi.org/10.1111/jpi.12814.</p><p>The BSO + GLUT image in Figure 5F was the same as the BSO + GLUT image in Figure 5H. The corrected image for Figure 5F is displayed here:</p><p>We apologize for this error.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70024","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142891083","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 Affects Peucedanum praeruptorum Vegetative Growth and Coumarin Synthesis by Modulating the Antioxidant System, Photosynthesis, and Endogenous Hormones","authors":"Xiaoting Wan,&nbsp;Yingyu Zhang,&nbsp;Guoyu Wang,&nbsp;Ranran Liao,&nbsp;Haoyu Pan,&nbsp;Cunwu Chen,&nbsp;Bangxing Han,&nbsp;Hui Deng,&nbsp;Cheng Song","doi":"10.1111/jpi.70018","DOIUrl":"10.1111/jpi.70018","url":null,"abstract":"<div>\u0000 \u0000 <p>The dried root of <i>Peucedanum praeruptorum</i> 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 <i>P. praeruptorum</i>. 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 <i>P. praeruptorum</i>. Different MT concentrations exert distinct regulatory effects on <i>P. praeruptorum</i> growth and the expression of genes related to coumarin synthesis. Treatment of <i>P. praeruptorum</i> 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 <i>N</i>-acetyltransferase, acetylserotonin <i>O</i>-methyltransferase, and caffeic acid <i>O</i>-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 <i>PAL1</i>, <i>C4H</i>, <i>4CL-3</i>, <i>C3H-1</i>, <i>F6H-1</i>, <i>CCoAMT</i>, <i>OMT-1</i>, <i>CYP71AJ1</i>, <i>CYP84A1-1</i>, <i>S8H-1</i>, <i>PT-1</i>, and <i>COSY-1</i>. These findings demonstrate that MT may improve <i>P. praeruptorum</i> growth and development while promoting the synthesis of coumarin components.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875879","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":"Melatonin Inhibits Endometriosis Growth via Specific Binding and Inhibition of EGFR Phosphorylation","authors":"Yiran Li,&nbsp;Sze-Wan Hung,&nbsp;Xu Zheng,&nbsp;Yang Ding,&nbsp;Tao Zhang,&nbsp;Zhouyurong Tan,&nbsp;Ruizhe Zhang,&nbsp;Yuezhen Lin,&nbsp;Yi Song,&nbsp;Yao Wang,&nbsp;Chi-Chiu Wang","doi":"10.1111/jpi.70022","DOIUrl":"10.1111/jpi.70022","url":null,"abstract":"<p>As a chronic gynecological disease, endometriosis is defined as the implantation of endometrial glands as well as stroma outside the uterine cavity. Proliferation is a major pathophysiology in endometriosis. Previous studies demonstrated a hormone named melatonin, which is mainly produced by the pineal gland, exerts a therapeutic impact on endometriosis. Despite that, the direct binding targets and underlying molecular mechanism have remained unknown. Our study revealed that melatonin treatment might be effective in inhibiting the growth of lesions in endometriotic mouse model as well as in human endometriotic cell lines. Additionally, the drug–disease protein–protein interaction (PPI) network was built, and epidermal growth factor receptor (EGFR) was identified as a new binding target of melatonin treatment in endometriosis. Computational simulation together with BioLayer interferometry was further applied to confirm the binding affinity. Our result also showed melatonin inhibited the phosphorylation level of EGFR not only in endometriotic cell lines but also in mouse models. Furthermore, melatonin inhibited the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)—protein kinase B (Akt) pathway and arrested the cell cycle via inhibiting CyclinD1 (CCND1). In vitro and in vivo knockdown/restore assays further demonstrated the involvement of the binding target and signaling pathway that we found. Thus, melatonin can be applied as a novel therapy for the management of endometriosis.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664468/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875933","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":"Zebrafish Dark-Dependent Behavior Requires Phototransduction by the Pineal Gland","authors":"Yair Wexler,&nbsp;Dengfeng Huang,&nbsp;Adar Medvetzky,&nbsp;Daniel Armbruster,&nbsp;Wolfgang Driever,&nbsp;Jun Yan,&nbsp;Yoav Gothilf","doi":"10.1111/jpi.70021","DOIUrl":"10.1111/jpi.70021","url":null,"abstract":"<p>Located dorsally underneath a thin translucent skull in many teleosts, the pineal gland is a photoreceptive organ known as a key element of the circadian clock system. Nevertheless, the presence of additional routes of photoreception presents a challenge in determining its specific roles in regulating photic-related behavior. Here, we show the importance of the pineal gland in mediating a prolonged motor response of zebrafish larvae to sudden darkness, both as a photodetector and as a circadian pacemaker. This was evident by a reduced motor response of Bsx-deficient larvae, lacking a pineal gland, to sudden darkness. Moreover, the typical daily rhythm of the intensity of this response was lost in the pineal-less larvae. In contrast, motor response to a sudden increase in illumination was unaffected. Furthermore, we show that the pineal-mediated behavioral response to darkness requires two elements: the photoreceptor cells and the projecting neurons. Dark response was impaired in larvae whose pineal photoreceptor cells were genetically ablated and in larvae whose pineal projecting neurons had undergone laser-axotomy. This study thus establishes the pineal gland as a mediator of dark-dependent behavior and reveals underlying cellular components involved in transducing information about darkness to the brain.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11664460/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142875939","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":"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}