Journal of Pineal Research最新文献

{"title":"From Seasonality to Species Conservation: Chronobiological Research on European Hamsters in Strasbourg, France","authors":"Stefanie Monecke","doi":"10.1111/jpi.13012","DOIUrl":"https://doi.org/10.1111/jpi.13012","url":null,"abstract":"<p>The first monograph on the European hamster from the Strasbourg region dates back to 1765. By the 1930s, a long and continuous chronobiological research tradition was established for this species, starting with the works of Charles Kayser, who published between 1938 and 1971. Another early key researcher in this area was Bernhard Canguilhem with publications from 1966 to 1999. From the 1980s onwards, “the Pévets,” Paul Pévet and his wife, Mireille Masson-Pévet, gave new energy to European hamster research. They broadened the research scope from basic hibernation research to mechanistic studies of circannual rhythms and from physiological aspects to molecular details. One main underlying question in their research was the role of melatonin. Thanks to their enthusiasm and vision, the European hamster is today one of the best – if not the best – studied circannual species. At least 73 parameters are described to cycle. Thirty-two of them have been shown to be driven by a circannual clock. Moreover, ground-breaking advances in our understanding of the mechanistic of hibernation, circannual clock functioning, and its entrainment were made. With most of this research being conducted in Strasbourg, Paul Pévet was instrumental in providing the necessary resources that made these innovative and unconventional long-term animal studies possible, contributing to fundamental research and, ultimately, to species conservation.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 7","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.13012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447762","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":"RETRACTION: Effects of Melatonin on Fatty Liver Disease: The Role of NR4A1/DNA-Pkcs/P53 Pathway, Mitochondrial Fission, and Mitophagy","authors":"","doi":"10.1111/jpi.70001","DOIUrl":"https://doi.org/10.1111/jpi.70001","url":null,"abstract":"<p><b>RETRACTION:</b> H. Zhou, W. Du, Y. Li, C. Shi, N. Hu, S. Ma, W. Wang, and J. Ren, “Effects of Melatonin on Fatty Liver Disease: The Role of NR4A1/DNA-Pkcs/P53 Pathway, Mitochondrial Fission, and Mitophagy,” <i>Journal of Pineal Research</i> 64, no. 1 (2018): e12450, https://doi.org/10.1111/jpi.12450.</p><p>The above article, published online on 05 October 2017, in Wiley Online Library (wileyonlinelibrary.com) and its correction (https://doi.org/10.1111/jpi.12946) have been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini, and John Wiley and Sons Ltd. The retraction has been agreed upon following an investigation into additional concerns raised by a third party regarding the scientific integrity of the generation of DNA-PKcsfl/fl mouse model and the reliability of the data presented in Figure 4 A and J, Figure 5E-G and Figure 7A and E. The original raw data was not available upon request from the authors. The senior corresponding author's institute stated that the study was not conducted at their university. Given the extent of the identified issues, the editors have lost confidence in the data presented and the article's conclusions can no longer be considered reliable. The first author disagrees with the retraction, and all other authors remained unresponsive.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 7","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70001","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447761","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 Inhibits ET-1 Production to Break Crosstalk Between Prostate Cancer and Bone Cells: Implication for Osteoblastic Bone Metastasis Treatment","authors":"Liang-Wei Lin,&nbsp;Tien-Huang Lin,&nbsp;Sanskruti Swain,&nbsp;Jen-Kai Fang,&nbsp;Jeng-Hung Guo,&nbsp;Shun-Fa Yang,&nbsp;Chih-Hsin Tang","doi":"10.1111/jpi.70000","DOIUrl":"https://doi.org/10.1111/jpi.70000","url":null,"abstract":"<div>\u0000 \u0000 <p>Bone metastasis is the primary cause of death among patients with advanced prostate cancer (PCa). PCa tends to spread to bones and acquire the bone-like phenotype, causing osteoblastic bone metastasis. Unfortunately, there is no effective treatment for this condition. However, melatonin, which regulates our circadian rhythm, has been found to have anti-tumor properties. It has yet to be established whether it is effective in treating osteoblastic PCa metastasis. Our findings show that melatonin inhibits the production of endothelin-1 (ET-1) in osteoblastic PCa cells, suppressing osteoblast differentiation. Clinical results indicate that bone metastatic PCa patients have higher levels of ET-1 compared to nonmetastatic PCa patients. Furthermore, melatonin-induced miR-let-7f-5p inhibits ET-1-promoted osteoblast differentiation in osteoblastic PCa. Melatonin also suppresses the property of osteomimicry in osteoblastic PCa cells. Importantly, in the intratibia injection PCa metastasis model, melatonin decreased osteoblastic PCa tumor growth, inhibiting ET-1 production and osteoblast differentiation in vivo. Taken together, melatonin inhibits osteoblastic PCa-regulated osteoblastogenesis by reducing ET-1 production through upregulation of miR-let-7f-5p, while suppressing the property of osteomimicry in osteoblastic PCa. Melatonin therapy could be a promising approach to treating bone metastasis in osteoblastic PCa.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 7","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142447763","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, Melatonin Receptors and Sleep: Moving Beyond Traditional Views","authors":"Stefano Comai,&nbsp;Gabriella Gobbi","doi":"10.1111/jpi.13011","DOIUrl":"https://doi.org/10.1111/jpi.13011","url":null,"abstract":"<p>Sleep, constituting approximately one-third of the human lifespan, is a crucial physiological process essential for physical and mental well-being. Normal sleep consists of an orderly progression through wakefulness, non-rapid eye movement (NREM) sleep, and rapid eye movement (REM) sleep, all of which are tightly regulated. Melatonin, often referred to as the “hormone of sleep,” plays a pivotal role as a regulator of the sleep/wake cycle and exerts its effects through high-affinity G-protein coupled receptors known as MT1 and MT2. Selective modulation of these receptors presents a promising therapeutic avenue for sleep disorders. This review examines research on the multifaceted role of melatonin in sleep regulation, focusing on selective ligands targeting MT1 and MT2 receptors, as well as studies involving MT1 and MT2 knockout mice. Contrary to common beliefs, growing evidence suggests that melatonin, through MT1 and MT2 receptors, might not only influence circadian aspects of sleep but likely, also modulate the homeostatic process of sleep and sleep architecture, or could be the molecule linking the homeostatic and circadian regulation of sleep. Furthermore, the distinct brain localization of MT1 and MT2 receptors, with MT1 receptors primarily regulating REM sleep and MT2 receptors regulating NREM sleep, is discussed. Collectively, sleep regulation extends beyond the circulating levels and circadian peak of melatonin; it also critically involves the expression, molecular activation, and regulatory functions of MT1 and MT2 receptors across various brain regions and nuclei involved in the regulation of sleep. This research underscores the importance of ongoing investigation into the selective roles of MT1 and MT2 receptors in sleep. Such research efforts are expected to pave the way for the development of targeted MT1 or MT2 receptors ligands, thereby optimizing therapeutic interventions for sleep disorders.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 7","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.13011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435646","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":"Differential Effects of Light and Dark Phase Modifications on Jet Lag Adaptability in Mice","authors":"Changxiao Ma,&nbsp;Haonan Li,&nbsp;Bingyi Shen,&nbsp;Huiwen Zheng,&nbsp;Yunfei Chen,&nbsp;Lihong Chen,&nbsp;Guangrui Yang","doi":"10.1111/jpi.13010","DOIUrl":"https://doi.org/10.1111/jpi.13010","url":null,"abstract":"<p>In chronobiology, shifting light/dark cycles is a common method to disrupt circadian rhythms. While the direction and magnitude of a phase shift (e.g., +6 denoting a 6-h advanced shift) dictate the temporal change before and after the shift, little attention has been paid to the duration and relative proportion of daytime and nighttime during the shift, leading to a critical, unexamined variable in circadian research. In this study, we introduce the concepts of “L-shift” (longer light phase on the shift day) and “D-shift” (longer dark phase), and investigate how these variations impact the adaptability of mice to jet lag. By examining multiple phase shifts (12L vs. 12D, +6L vs. +6D, −6L vs. −6D), we demonstrate that L-shifts not only facilitate faster adaptation but also significantly reduce the severity of sepsis in a jet lag-sensitive lipopolysaccharide-induced sepsis model. Further investigations with additional phase shifts at 1-h intervals (+8 to +11) reinforced the enhanced fitness of mice under L-shifts. Mechanistically, L-shifts were found to increase sleep duration, thereby improving circadian entrainment, with sleep deprivation nullifying the adaptability differences between lighting protocols. These findings underscore a previously unrecognized factor in circadian biology and suggest that optimizing lighting protocols could profoundly improve adaptability to circadian disruptions. This research opens new avenues for enhancing therapeutic strategies and refining experimental designs in the field of chronobiology.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 7","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.13010","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142435648","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 Regulates Rheumatoid Synovial Fibroblasts-Related Inflammation: Implications for Pathological Skeletal Muscle Treatment","authors":"Chen-Ming Su,&nbsp;Chun-Hao Tsai,&nbsp;Hsien-Te Chen,&nbsp;Yi-Syuan Wu,&nbsp;Shun-Fa Yang,&nbsp;Chih-Hsin Tang","doi":"10.1111/jpi.13009","DOIUrl":"10.1111/jpi.13009","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin has been reported to regulate circadian rhythms and have anti-inflammatory characteristics in various inflammatory autoimmune diseases, but its effects in diseases-associated muscle atrophy remain controversial. This study is aimed to determine the evidence of melatonin in rheumatoid arthritis (RA)-related pathological muscle atrophy. We used initially bioinformatics results to show that melatonin regulated significantly the correlation between pro-inflammation and myogenesis in RA synovial fibroblasts (RASF) and myoblasts. The conditioned medium (CM) from melatonin-treated RASF was incubated in myoblasts with growth medium and differentiated medium to investigate the markers of pro-inflammation, atrophy, and myogenesis. We found that melatonin regulated RASF CM-induced pathological muscle pro-inflammation and atrophy in myoblasts and differentiated myocytes through NF-κB signaling pathways. We also showed for the first time that miR-30c-1-3p is negatively regulated by three inflammatory cytokines in human RASF, which is associated with murine-differentiated myocytes. Importantly, oral administration with melatonin in a collagen-induced arthritis (CIA) mouse model also significantly improved arthritic swelling, hind limb grip strength as well as pathological muscle atrophy. In conclusion, our study is the first to demonstrate not only the underlying mechanism whereby melatonin decreases pro-inflammation in RA-induced pathological muscle atrophy but also increases myogenesis in myoblasts and differentiated myocytes.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142306800","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 Attenuates Diabetic Retinopathy by Regulating EndMT of Retinal Vascular Endothelial Cells via Inhibiting the HDAC7/FOXO1/ZEB1 Axis","authors":"Jiayi Ning,&nbsp;Minghong Pan,&nbsp;Hanyi Yang,&nbsp;Zhaoyang Wang,&nbsp;Xiaolan Wang,&nbsp;Kai Guo,&nbsp;Yingtong Feng,&nbsp;Tingke Xie,&nbsp;Yixuan Chen,&nbsp;Chengming Chen,&nbsp;Sida Liu,&nbsp;Yimeng Zhang,&nbsp;Yuanyong Wang,&nbsp;Xiaolong Yan,&nbsp;Jing Han","doi":"10.1111/jpi.13008","DOIUrl":"https://doi.org/10.1111/jpi.13008","url":null,"abstract":"<div>\u0000 \u0000 <p>Diabetic retinopathy (DR) is characterized as a microvascular disease. Nonproliferative diabetic retinopathy (NPDR) presents with alterations in retinal blood flow and vascular permeability, thickening of the basement membrane, loss of pericytes, and formation of acellular capillaries. Endothelial–mesenchymal transition (EndMT) of retinal microvessels may play a critical role in advancing NPDR. Melatonin, a hormone primarily secreted by the pineal gland, is a promising therapeutic for DR. This study explored the EndMT in retinal microvessels of NPDR and its related mechanisms. The effect of melatonin on the retina of diabetic rats was evaluated by electroretinogram (ERG) and histopathologic slide staining. Furthermore, the effect of melatonin on human retinal microvascular endothelial cells (HRMECs) was detected by EdU incorporation assay, scratch assay, transwell assay, and tube formation test. Techniques such as RNA-sequencing, overexpression or knockdown of target genes, extraction of cytoplasmic and nuclear protein, co-immunoprecipitation (co-IP), and multiplex immunofluorescence facilitated the exploration of the mechanisms involved. Our findings reveal, for the first time, that melatonin attenuates diabetic retinopathy by regulating EndMT of retinal vascular endothelial cells via inhibiting the HDAC7/FOXO1/ZEB1 axis. Collectively, these results suggest that melatonin holds potential as a therapeutic strategy to reduce retinal vascular damage and protect vision in NPDR.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-09-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142273227","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 Prevents Thioacetamide–Induced Gut Leakiness and Liver Fibrosis Through the Gut–Liver Axis via Modulating Sirt1-Related Deacetylation of Gut Junctional Complex and Hepatic Proteins","authors":"Wiramon Rungratanawanich,&nbsp;Karli Rae LeFort,&nbsp;Young-Eun Cho,&nbsp;Xiaoling Li,&nbsp;Byoung-Joon Song","doi":"10.1111/jpi.13007","DOIUrl":"https://doi.org/10.1111/jpi.13007","url":null,"abstract":"<p>Intestinal barrier dysfunction with high serum endotoxin is common in patients with liver fibrosis, but the mechanisms underlying liver fibrosis remain unclear. Melatonin is a well-recognized antioxidant and an anti-inflammatory agent that benefits multiple organs. However, the beneficial effects of melatonin on gut leakiness–associated liver fibrosis have not been systemically studied. Here, we investigated the protective mechanisms of melatonin against thioacetamide (TAA)–induced gut barrier dysfunction and hepatic fibrosis by focusing on posttranslational protein modifications through the gut–liver axis. Our results showed that gut leakiness markers, including decreased gut tight/adherens junction proteins (TJ/AJs) with increased intestinal deformation, apoptosis, and serum endotoxin, were observed early at 1 week after TAA exposure. Liver injury, apoptosis, and fibrosis were prominent at 2 and 4 weeks. Mechanistically, we found that gut TJ/AJs were hyper-acetylated, followed by ubiquitin-dependent proteolysis, leading to their degradation and gut leakiness. Gut dysbiosis, hepatic protein hyper-acetylation, and SIRT1 downregulation were also observed. Consistently, intestinal <i>Sirt1</i> deficiency greatly enhanced protein hyper-acetylation, gut leakiness, endotoxemia, and liver fibrosis. Pretreatment with melatonin prevented or improved all these changes in both the gut and liver. Furthermore, melatonin blunted protein acetylation and injury in TAA–exposed T84 human intestinal and AML12 mouse liver cells. Overall, this study demonstrated novel mechanisms by which melatonin prevents gut leakiness and liver fibrosis through the gut–liver axis by attenuating the acetylation of intestinal and hepatic proteins. Thus, melatonin consumption can become a potentially safe supplement for liver fibrosis patients by preventing protein hyper-acetylation and gut leakiness.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.13007","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142230950","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 Osteoarthritis by Regulating NADPH Oxidase 4–Induced Ferroptosis and Mitigating Mitochondrial Dysfunction","authors":"Qi Wang,&nbsp;Beijie Qi,&nbsp;Shi Shi,&nbsp;Weihao Jiang,&nbsp;Dejian Li,&nbsp;Xinhua Jiang,&nbsp;Chengqing Yi","doi":"10.1111/jpi.12992","DOIUrl":"10.1111/jpi.12992","url":null,"abstract":"<div>\u0000 \u0000 <p>Recent evidence indicates that the damaged regions in osteoarthritis are accompanied by the accumulation of iron ions. Ferroptosis, as an iron-dependent form of cell death, holds significant implications in osteoarthritis. Melatonin, a natural product with strong scavenging abilities against reactive oxygen species and lipid peroxidation, plays a crucial role in the treatment of osteoarthritis. This study aims to demonstrate the existence of ferroptosis in osteoarthritis and explore the specific mechanism of melatonin in suppressing ferroptosis and alleviating osteoarthritis. Our findings reveal that melatonin reverses inflammation-induced oxidative stress and lipid peroxidation while promoting the expression of extracellular matrix components in chondrocytes, safeguarding the cells. Our research has revealed that NADPH oxidase 4 (NOX4) serves as a crucial molecule in the ferroptosis process of osteoarthritis. Specifically, NOX4 is located on mitochondria in chondrocytes, which can induce disorders in mitochondrial energy metabolism and dysfunction, thereby intensifying oxidative stress and lipid peroxidation. LC-MS analysis further uncovered that GRP78 is a downstream binding protein of NOX4. NOX4 induces ferroptosis by weakening GRP78's protective effect on GPX4 and reducing its expression. Melatonin can inhibit the upregulation of NOX4 on mitochondria and mitigate mitochondrial dysfunction, effectively suppressing ferroptosis and alleviating osteoarthritis. This suggests that melatonin therapy represents a promising new approach for the treatment of osteoarthritis.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142124377","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 Regulates Neuronal Synaptic Plasticity in the Supramammillary Nucleus and Attenuates Methamphetamine-Induced Conditioned Place Preference and Sensitization in Mice","authors":"Qingyu Ren,&nbsp;Weikai Han,&nbsp;Yanan Yue,&nbsp;Yaqi Tang,&nbsp;Qingwei Yue,&nbsp;Stefano Comai,&nbsp;Jinhao Sun","doi":"10.1111/jpi.13006","DOIUrl":"10.1111/jpi.13006","url":null,"abstract":"<div>\u0000 \u0000 <p>Methamphetamine (METH) is an addictive drug that threatens human health. The supramammillary nucleus (SuM) and its neural circuits play key roles in the regulation of spatial memory retrieval, and hippocampal contextual or social memory. Melatonin (MLT), a pineal hormone, can regulate hypothalamic-neurohypophysial activity. Our previous study showed that MLT attenuates METH-induced locomotor sensitization. However, whether MLT regulates SuM function and participates in METH-induced contextual memory retrieval remains unclear. Using a mouse model of METH-conditioned place preference (CPP) and sensitization, we found that METH activated c-Fos expression and elevated calcium (Ca²⁺) levels in SuM neurons. Chemogenetic inhibition of SuM attenuates CPP and sensitization. Pretreatment with MLT decreased c-Fos expression and Ca²⁺ levels in the SuM and reversed METH-induced addictive behavior, effects that were blocked with the selective MT₂ receptors antagonist 4P-PDOT and the MT₁ receptors antagonist S26131. Furthermore, MLT reduced SuM synaptic plasticity, glutamate (Glu) release, and neuronal oscillations caused by METH, which were blocked by 4P-PDOT. In conclusion, our data revealed that MLT regulates neuronal synaptic plasticity in the SuM, likely through the MLT receptors (MTs), and plays a role in modulating METH-addictive behavior.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 6","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142102696","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}