Journal of Pineal Research最新文献

{"title":"Melatonin Ameliorates Cadmium-Induced Liver Fibrosis Via Modulating Gut Microbiota and Bile Acid Metabolism","authors":"Xianjiao Liu,&nbsp;Weili Kang,&nbsp;Jinyan Li,&nbsp;Xin Li,&nbsp;Peng Yang,&nbsp;Mengdie Shi,&nbsp;Zhongyu Wang,&nbsp;Yanyan Wang,&nbsp;Andrea Del Pilar Abreo Medina,&nbsp;Dandan Liu,&nbsp;Fenxia Zhu,&nbsp;Hong Shen,&nbsp;Kehe Huang,&nbsp;Xingxiang Chen,&nbsp;Yunhuan Liu","doi":"10.1111/jpi.70005","DOIUrl":"10.1111/jpi.70005","url":null,"abstract":"<div>\u0000 \u0000 <p>Cadmium (Cd) is a widespread environmental contaminant with high toxicity to human health. Melatonin has been shown to improve Cd-induced liver damage. However, its mechanism has not yet been elucidated. In this study, we aimed to investigate the effects of melatonin on Cd-induced liver damage and fibrosis. A combination of 16S rRNA gene sequencing and mass spectrometry-based metabolomics was adopted to investigate changes in the gut microbiome and its metabolites on the regulation of melatonin in Cd-induced liver injury and fibrosis of mice. Further, nonabsorbable antibiotics, a fecal microbiota transplantation (FMT) program and intestine-specific farnesoid X receptor (FXR) knockout mice were employed to explore the mechanism of melatonin (MT) on liver injury and fibrosis in Cd treated mice. MT significantly improved hepatic inflammation, bile duct hyperplasia, liver damage, and liver fibrosis, with a notable decrease in liver bile acid levels in Cd-exposed mice. MT treatment remodeled the gut microbiota, improved gut barrier function, and reduced the production of gut-derived lipopolysaccharide (LPS). MT significantly decreased the intestinal tauro-β-muricholic acid levels, which are known as FXR antagonists. Notably, MT prominently activated the intestinal FXR signaling, subsequently inhibiting liver bile acid synthesis and decreasing hepatic inflammation in Cd-exposed mice. However, MT could not ameliorate Cd-induced liver damage and fibrosis in Abx-treated mice. Conversely, MT still exerted a protective effect on Cd-induced liver damage and fibrosis in FMT mice. Interestingly, MT failed to reverse liver damage and fibrosis in Cd-exposed intestinal epithelial cell-specific FXR gene knockout mice, indicating that intestinal FXR signaling mediated the protective effect of MT treatment. MT improves Cd-induced liver damage and fibrosis through reshaping the intestinal flora, activating the intestinal FXR-mediated suppression of liver bile acid synthesis and reducing LPS leakage in mice.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142646362","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":"Timing Matters: Late, but Not Early, Exercise Training Ameliorates MASLD in Part by Modulating the Gut-Liver Axis in Mice","authors":"Artemiy Kovynev,&nbsp;Zhixiong Ying,&nbsp;Sen Zhang,&nbsp;Emanuele Olgiati,&nbsp;Joost M. Lambooij,&nbsp;Clara Visentin,&nbsp;Bruno Guigas,&nbsp;Quinten R. Ducarmon,&nbsp;Patrick C. N. Rensen,&nbsp;Milena Schönke","doi":"10.1111/jpi.70003","DOIUrl":"10.1111/jpi.70003","url":null,"abstract":"<p>Metabolic dysfunction-associated steatotic liver disease (MASLD) affects two billion people worldwide and is currently mostly treatable via lifestyle interventions, such as exercise training. However, it is unclear whether the positive effects of exercise are restricted to unique circadian windows. We therefore aimed to study whether the timing of exercise training differentially modulates MASLD development. Twenty weeks old male APOE*3-Leiden.CETP mice were fed a high fat-high cholesterol diet to induce MASLD and treadmill-trained for 1 h five times per week for 12 weeks either early (ZT13; E-RUN) or late (ZT22; <span>L</span>-RUN) in the dark phase while corresponding sedentary groups (E-SED and L-SED) did not. Late, but not early exercise training decreased the MASLD score, body weight, fat mass, and liver triglycerides, accompanied by an altered composition of the gut microbiota. Specifically, only late exercise training increased the abundance of short-chain fatty acid-producing bacterial families and genera, such as <i>Akkermansia, Lachnospiraceae</i>, and <i>Rikenella</i>. To assess the role of the gut microbiota in training-induced effects, the study was repeated and trained (ZT22 only, RUN) or sedentary mice (SED) served as fecal donors for sedentary recipient mice (RUN FMT and SED FMT). Fecal microbiota transplantation reduced liver weight and plasma triglycerides in RUN FMT compared to SED FMT and tended to lower the MASLD score and liver triglycerides. Timing of exercise training is a critical factor for the positive effect on MASLD in this preclinical model, and the effect of late exercise is partially mediated via the gut-liver axis.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70003","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613146","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 Protects Against Cocaine-Induced Blood−Brain Barrier Dysfunction and Cognitive Impairment by Regulating miR-320a-Dependent GLUT1 Expression","authors":"Jia-Yi Wei,&nbsp;Hui Liu,&nbsp;Yuan Li,&nbsp;Dan Zhao,&nbsp;Bo Wang,&nbsp;Hui-Jie Wang,&nbsp;Li Wang,&nbsp;Kang-Ji Wang,&nbsp;Jin-Li Yue,&nbsp;Hong-Yan Zhang,&nbsp;Tian-Yue Li,&nbsp;Yi-Jue Miao,&nbsp;Kai-Li Wang,&nbsp;Pai-Ge Tong,&nbsp;Zhuo Zhang,&nbsp;Ze-Ye Li,&nbsp;Zheng Shi,&nbsp;Jia-Yuan Yao,&nbsp;Dong-Xin Liu,&nbsp;Wen-Gang Fang,&nbsp;Bo Li,&nbsp;De-Shu Shang,&nbsp;Yuan Lyu,&nbsp;Hong-Zan Sun,&nbsp;Wei-Dong Zhao,&nbsp;Yu-Hua Chen","doi":"10.1111/jpi.70002","DOIUrl":"10.1111/jpi.70002","url":null,"abstract":"<div>\u0000 \u0000 <p>Cocaine abuse has been strongly linked to blood−brain barrier (BBB) dysfunction, though the exact mechanism by which cocaine disrupts the BBB remains unclear. In this study, we found that cocaine treatment reduces the expression of glucose transporter 1 (GLUT1) in brain microvascular endothelial cells, a key factor in cocaine-induced brain glucose uptake, BBB leakage, and cognitive impairment. Mechanistically, our results show that cocaine upregulates miR-320a, which in turn suppresses GLUT1 expression via the beta 2-adrenergic receptor (ADRB2). Notably, the administration of adeno-associated viruses encoding full-length GLUT1 or miR-320a inhibitors to the brain microvascular endothelium significantly mitigated cocaine-induced BBB leakage and cognitive deficits. Additionally, we discovered that melatonin, a well-known neuroprotective hormone, alleviates cocaine-induced BBB disruption and cognitive impairment. This protective effect of melatonin was mediated through the upregulation of miR-320a-dependent GLUT1 expression in brain endothelial cells via MT₁ receptor-mediated inhibition of the cAMP/PKA/CREB signaling pathway. In conclusion, our findings demonstrate that cocaine downregulates brain microvascular GLUT1, leading to BBB dysfunction, and highlight melatonin as a potential therapeutic agent for treating cocaine-related complications.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613145","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":"Disruption of Melatonin Signaling Leads to Lipids Accumulation in the Liver of Melatonin Proficient Mice","authors":"Varunika Goyal,&nbsp;Gianluca Tosini","doi":"10.1111/jpi.70007","DOIUrl":"10.1111/jpi.70007","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin signaling via melatonin receptor type 1 (MT₁) and type 2 (MT₂) plays an important role in the regulation of several physiological functions. Studies in rodents and humans have demonstrated that disruption of melatonin signaling may affect glucose metabolism, insulin sensitivity, and leptin levels. Accumulating experimental evidence also indicates that in rodents the administration of exogenous melatonin has a beneficial effect on the blood lipid levels. However, the molecular mechanism by which melatonin signaling may regulate lipids is still unclear. In addition, most of the studies with mice have been performed in melatonin-deficient mice by administering exogenous melatonin at supraphysiological doses. Hence the results of these studies may be greatly affected by these two factors. In this study, we report the effects of melatonin signaling removal on the liver biology and transcriptome using melatonin-proficient mice (C3H-f^+/f+) in which MT₁ or MT₂ have been genetically ablated. Our data indicate that the absence of MT₁ or MT₂ signaling leads to disruption of the blood lipids profile and an increase in lipids deposition in the liver. These effects were more pronounced in the mice lacking MT₁ than MT₂. The gene expression profiles obtained with RNA-seq from the livers of the three genotypes revealed that removal of MT₁ affected the transcription of 4255 genes (i.e., 40.6%). Conversely, the removal of MT₂ affected the transcription of 1864 transcripts (i.e., 17.2%). Finally, we identified a group of 13 genes involved in lipids biology that may play a key role in the accumulation of lipids in the liver when melatonin signaling is disrupted. In conclusion, our study indicates that melatonin signaling is an important modulator of liver physiology and metabolism. Our study also indicated that the removal of MT₁ signaling is more deleterious than MT₂ removal.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142613142","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":"Biosynthesis of neuroprotective melatonin is dysregulated in Huntington's disease","authors":"Jinho Kim,&nbsp;Wei Li,&nbsp;Jingjing Wang,&nbsp;Sergei V. Baranov,&nbsp;Brianna E. Heath,&nbsp;Jiaoying Jia,&nbsp;Yalikun Suofu,&nbsp;Oxana V. Baranova,&nbsp;Xiaomin Wang,&nbsp;Timothy M. Larkin,&nbsp;William R. Lariviere,&nbsp;Diane L. Carlisle,&nbsp;Robert M. Friedlander","doi":"10.1111/jpi.12909","DOIUrl":"10.1111/jpi.12909","url":null,"abstract":"<p>Huntington's disease (HD) is a progressive neurodegenerative brain disorder associated with uncontrolled body movements, cognitive decline, and reduced circulating melatonin levels. Melatonin is a potent antioxidant and exogenous melatonin treatment is neuroprotective in experimental HD models. In neurons, melatonin is exclusively synthesized in the mitochondrial matrix. Thus, we investigated the integrity of melatonin biosynthesis pathways in pineal and extrapineal brain areas in human HD brain samples, in the R6/2 mouse model of HD and in full-length mutant huntingtin knock-in cells. Aralkylamine N-acetyltransferase (AANAT) is the rate-limiting step enzyme in the melatonin biosynthetic pathway. We found that AANAT expression is significantly decreased in the pineal gland and the striatum of HD patients compared to normal controls. In the R6/2 mouse forebrain, AANAT protein expression was decreased in synaptosomal, but not nonsynaptosomal, mitochondria and was associated with decreased synaptosomal melatonin levels compared to wild type mice. We also demonstrate sequestration of AANAT in mutant-huntingtin protein aggregates likely resulting in decreased AANAT bioavailability. Paradoxically, <i>AANAT</i> mRNA expression is increased in tissues where AANAT protein expression is decreased, suggesting a potential feedback loop that is, ultimately unsuccessful. In conclusion, we demonstrate that pineal, extrapineal, and synaptosomal melatonin levels are compromised in the brains of HD patients and R6/2 mice due, at least in part, to protein aggregation.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"75 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2023-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10652947","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":"iMS-Bmal1−/− mice show evident signs of sarcopenia that are counteracted by exercise and melatonin therapies","authors":"José Fernández-Martínez,&nbsp;Yolanda Ramírez-Casas,&nbsp;Paula Aranda-Martínez,&nbsp;Alba López-Rodríguez,&nbsp;Ramy K. A. Sayed,&nbsp;Germaine Escames,&nbsp;Darío Acuña-Castroviejo","doi":"10.1111/jpi.12912","DOIUrl":"10.1111/jpi.12912","url":null,"abstract":"<p>Sarcopenia is an age-related disease characterized by a reduction in muscle mass, strength, and function and, therefore, a deterioration in skeletal muscle health and frailty. Although the cause of sarcopenia is still unknown and, thus, there is no treatment, increasing evidence suggests that chronodisruption, particularly alterations in <i>Bmal1</i> clock gene, can lead to those deficits culminating in sarcopenia. To gain insight into the cause and mechanism of sarcopenia and the protective effect of a therapeutic intervention with exercise and/or melatonin, the gastrocnemius muscles of male and female skeletal muscle-specific and inducible <i>Bmal1</i> knockout mice (iMS-<i>Bmal1</i>^{<i>−/−</i>}) were examined by phenotypic tests and light and electron microscopy. Our results revealed a disruption of the normal activity/rest rhythm, a drop in skeletal muscle function and mass, and increased frailty in male and female iMS-<i>Bmal1^−/−</i> animals compared to controls. A reduction in muscle fiber size and increased collagenous tissue were also detected, accompanied by reduced mitochondrial oxidative capacity and a compensatory shift towards a more oxidative fiber type. Electron microscopy further supports mitochondrial impairment in mutant mice. Melatonin and exercise ameliorated the damage caused by loss of <i>Bmal1</i> in mutant mice, except for mitochondrial damage, which was worsened by the latter. Thus, iMS-<i>Bmal1^−/−</i> mice let us to identify <i>Bmal1</i> deficiency as the responsible for the appearance of sarcopenia in the gastrocnemius muscle. Moreover, the results support the exercise and melatonin as therapeutic tools to counteract sarcopenia, by a mechanism that does not require the presence of <i>Bmal1</i>.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 1","pages":""},"PeriodicalIF":10.3,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12912","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10276830","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":"Primary Gamma Knife Radiosurgery for pineal region tumors: A systematic review and pooled analysis of available literature with histological stratification","authors":"Filippo Gagliardi,&nbsp;Pierfrancesco De Domenico,&nbsp;Enrico Garbin,&nbsp;Silvia Snider,&nbsp;Pietro Mortini","doi":"10.1111/jpi.12910","DOIUrl":"10.1111/jpi.12910","url":null,"abstract":"<p>Pineal region tumors (PTs) represent extremely rare pathologies, characterized by highly heterogeneous histological patterns. Most of the available evidence for Gamma Knife radiosurgical (GKSR) treatment of PTs arises from multimodal regimens, including GKSR as an adjuvant modality or as a salvage treatment at recurrence. We aimed to gather existing evidence on the topic and analyze single-patient-level data to address the efficacy and safety of primary GKSR. This is a systematic review of the literature (PubMed, Embase, Cochrane, Science Direct) and pooled analysis of single-patient-level data. A total of 1054 original works were retrieved. After excluding duplicates and irrelevant works, we included 13 papers (<i>n</i> = 64 patients). An additional 12 patients were included from the authors' original series. A total of 76 patients reached the final analysis; 56.5% (<i>n</i> = 43) received a histological diagnosis. Confirmed lesions included pineocytoma WHO grade I (60.5%), pineocytoma WHO grade II (14%), pineoblastoma WHO IV (7%), pineal tumor with intermediate differentiation WHO II/III (4.7%), papillary tumor of pineal region WHO II/III (4.7%), germ cell tumor (2.3%), neurocytoma WHO I (2.3%), astrocytoma WHO II (2.3%) and WHO III (2.3%). Presumptive diagnoses were achieved in the remaining 43.5% (<i>n</i> = 33) of cases and comprised of pineocytoma (9%), germ cell tumor (6%), low-grade glioma (6%), high-grade glioma (3%), meningioma (3%) and undefined in 73%. The mean age at the time of GKSR was 38.7 years and the mean lesional volume was 4.2 ± 4 cc. All patients received GKSR with a mean marginal dose of 14.7 ± 2.1 Gy (50% isodose). At a median 36-month follow-up, local control was achieved in 80.3% of cases. Thirteen patients showed progression after a median time of 14 months. Overall mortality was 13.2%. The median OS was not reached for all included lesions, except high-grade gliomas (8mo). The 3-year OS was 100% for LGG and pineal tumors with intermediate differentiation, 91% for low-grade pineal lesions, 66% for high-grade pineal lesions, 60% for germ cell tumors (GCTs), 50% for HGG, and 82% for undetermined tumors. The 3-year progression-free survival (PFS) was 100% for LGG and pineal intermediate tumors, 86% for low-grade pineal, 66% for high-grade pineal, 33.3% for GCTs, and 0% for HGG. Median PFS was 5 months for HGG and 34 months for GCTs. The radionecrosis rate was 6%, and cystic degeneration was observed in 2%. Ataxia as a presenting symptom strongly predicted mortality (odds ratio [OR] 104, <i>p</i> = .02), while GCTs and HGG histology well predicted PD (OR: 13, <i>p</i> = .04). These results support the efficacy and safety of primary GKSR treatment of PTs. Further studies are needed to validate these results, which highlight the importance of the initial presumptive diagnosis for choosing the best therapeutic strategy.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"75 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12910","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10229988","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":"Correction to human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential","authors":"","doi":"10.1111/jpi.12911","DOIUrl":"10.1111/jpi.12911","url":null,"abstract":"<p>Huo X, Wang C, Yu Z, Peng Y, Wang S, Feng S, Zhang S, Tian X, Sun C, Liu K, Deng S, Ma X. Human transporters, PEPT1/2, facilitate melatonin transportation into mitochondria of cancer cells: An implication of the therapeutic potential. <i>J Pineal Res</i>. 2017;62(4):12390. https://doi.org/10.1111/jpi.12390</p><p>In Figure 10B, the C-casp3 bands of PC3 cells and Bax bands of U118 cells were accidentally wrongly used during the figure preparation. The corrected figures are provided below.</p><p>This corrected figure does not change the conclusions of this study. This correction does not modify the data interpretation of the original article. We apologize for this error.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 3","pages":""},"PeriodicalIF":10.3,"publicationDate":"2023-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12911","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10193917","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":"From gestational chronodisruption to noncommunicable diseases: Pathophysiological mechanisms of programming of adult diseases, and the potential therapeutic role of melatonin","authors":"Natalia Méndez,&nbsp;Fernando Corvalan,&nbsp;Diego Halabi,&nbsp;Pamela Ehrenfeld,&nbsp;Rodrigo Maldonado,&nbsp;Karina Vergara,&nbsp;Maria Seron-Ferre,&nbsp;Claudia Torres-Farfan","doi":"10.1111/jpi.12908","DOIUrl":"10.1111/jpi.12908","url":null,"abstract":"<p>During gestation, the developing fetus relies on precise maternal circadian signals for optimal growth and preparation for extrauterine life. These signals regulate the daily delivery of oxygen, nutrients, hormones, and other biophysical factors while synchronizing fetal rhythms with the external photoperiod. However, modern lifestyle factors such as light pollution and shift work can induce gestational chronodisruption, leading to the desynchronization of maternal and fetal circadian rhythms. Such disruptions have been associated with adverse effects on cardiovascular, neurodevelopmental, metabolic, and endocrine functions in the fetus, increasing the susceptibility to noncommunicable diseases (NCDs) in adult life. This aligns with the Developmental Origins of Health and Disease theory, suggesting that early-life exposures can significantly influence health outcomes later in life. The consequences of gestational chronodisruption also extend into adulthood. Environmental factors like diet and stress can exacerbate the adverse effects of these disruptions, underscoring the importance of maintaining a healthy circadian rhythm across the lifespan to prevent NCDs and mitigate the impact of gestational chronodisruption on aging. Research efforts are currently aimed at identifying potential interventions to prevent or mitigate the effects of gestational chronodisruption. Melatonin supplementation during pregnancy emerges as a promising intervention, although further investigation is required to fully understand the precise mechanisms involved and to develop effective strategies for promoting health and preventing NCDs in individuals affected by gestational chronodisruption.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"75 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12908","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10122625","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":"The mammalian gastro-intestinal tract is a NOT a major extra-pineal source of melatonin","authors":"David J. Kennaway","doi":"10.1111/jpi.12906","DOIUrl":"10.1111/jpi.12906","url":null,"abstract":"<p>In 1992, a paper reported that the melatonin content of the rat duodenum was 24 000 ± 2000 pg/g tissue (range: 4000–100 000 pg/g) while the pineal melatonin content was 580 000 ± 36 000 pg/g. The data has been used for the last 30 years to infer that the gut produces 400 hundred times more melatonin than the pineal gland and that it is the source of plasma melatonin during the daytime. No-one has ever challenged the statement. In this review, evidence is summarised from the literature that pinealectomy eliminates melatonin from the circulation and that studies to the contrary have relied upon poorly validated immunoassays that overstate the levels. Similarly studies that have reported increases in plasma melatonin following tryptophan administration failed to account for cross reactivity of tryptophan and its metabolites in immunoassays. The most extraordinary observation from the literature is that in those studies that have measured melatonin in the gut since 1992, the tissue content is vastly lower than the original report, even when the methodology used could be overestimating the melatonin content due to cross reactivity. Using the more contemporary results we can calculate that rather than a 400:1 ratio of duodenum: pineal melatonin, a ratio of 0.05–0.19: 1 is likely. The gut is not a major extra-pineal source of melatonin; indeed it may well not produce any.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"75 4","pages":""},"PeriodicalIF":10.3,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.12906","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10142390","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}