Journal of Pineal Research最新文献

{"title":"Parkin-TLR4-NLRP3 Axis Directs Melatonin to Alleviate Atrazine-Induced Immune Impairment in Splenic Macrophages","authors":"Shuo Liu,&nbsp;Tian-Ning Yang,&nbsp;Yu-Xiang Wang,&nbsp;Xiang-Yu Ma,&nbsp;Yu-Sheng Shi,&nbsp;Yi Zhao,&nbsp;Jin-Long Li","doi":"10.1111/jpi.70014","DOIUrl":"10.1111/jpi.70014","url":null,"abstract":"<div>\u0000 \u0000 <p>Atrazine (ATR) is a widespread environmental herbicide that seriously affects agricultural work and human safety. Melatonin (MLT) as an endogenous neuroendocrine hormone is widely found in animals and plants, which have antioxidant and anti-inflammatory effects. Pink1/Parkin-mediated mitophagy keeps normal physiological processes by degrading damaged mitochondria in cells. Therefore, we investigated the potential role and mechanism of MLT in ATR-induced toxic injury of the spleen. The results showed that MLT alleviated ATR-induced unclear boundary between the white pulp and the red pulp of the spleen. It is also shown that ATR resulted in swollen mitochondria, partial extinction of mitochondrial membranes and cristae, and increased mitophagy under the action of MLT. ATR-induced reactive oxygen species (ROS) activates the Pink1/Parkin pathway, which guides mitophagy development and then causes the activation of TLR4/NF-κB inflammatory pathway. Meanwhile, these damages further exacerbated the production of NLRP3 inflammasomes, leading to spleen necrosis. Interestingly, these changes were improved after MLT treatment. Collectively, we found that MLT alleviates ATR-induced immune impairment in splenic macrophages via regulating Parkin-TLR4-NLRP3 axis which elucidates the effect of melatonin on the spleen and provides a novel perspective on melatonin in splenic inflammatory injury treatment.</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":"142793944","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":"OPA1 Mediated Fatty Acid β-Oxidation in Hepatocyte: The Novel Insight for Melatonin Attenuated Apoptosis in Concanavalin A Induced Acute Liver Injury","authors":"Tong Chen,&nbsp;Ruonan Shuang,&nbsp;Tiantian Gao,&nbsp;Lijun Ai,&nbsp;Jichen Diao,&nbsp;Xinyi Yuan,&nbsp;Ling He,&nbsp;Weiwei Tao,&nbsp;Xin Huang","doi":"10.1111/jpi.70010","DOIUrl":"https://doi.org/10.1111/jpi.70010","url":null,"abstract":"<div>\u0000 \u0000 <p>Melatonin (MLT) has been reported to attenuate Concanavalin A (Con A)-induced acute liver injury via the inhibition of immune cells. Whereas the response of hepatocyte to Con A-caused inflammatory storm and the mechanism of MLT on hepatocyte remain not fully understood. Our RNA-seq and bioinformatic analyses suggested that OPA1 and fatty acid β-oxidation might be critical. It was found that MLT ameliorated Con A-induced acute liver injury, promoted mitochondrial fusion, fatty acid β-oxidation, modulated metabolic reprogramming and inhibited apoptosis. The overexpression and knockdown of OPA1 by adenovirus proved that these processes were governed by OPA1. With the overexpression plasmid, agonist, inhibitor and SiRNA, we found that MLT promoted OPA1 upregulation to enhance fatty acid β-oxidation, which inhibited apoptosis. The MLT and OPA1-promoted fatty acid β-oxidation enhanced ATP production rather than reduced lipid accumulation. AMPK/FOXO1 was required for MLT and OPA1-mediated fatty acid β-oxidation and apoptosis. NOTCH1 was also necessary for this apoptotic process. The results were verified in immune deficiency mice and AML12 cells induced by Con A-stimulated monocyte supernatant. MLT might control the transcription of OPA1 through MEF2A. TOMM70 was critical for MLT translocation and OPA1 upregulation. In conclusion, the present study demonstrated that MLT attenuated Con A-induced acute liver injury via the OPA1-controlled fatty acid β-oxidation to inhibit apoptosis in hepatocyte.</p></div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142759855","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":"RETRACTION: Regulation of Prostaglandin Production in Carrageenan-Induced Pleurisy Melatonin","authors":"","doi":"10.1111/jpi.70011","DOIUrl":"https://doi.org/10.1111/jpi.70011","url":null,"abstract":"<p><b>RETRACTION:</b> S. Cuzzocrea, G. Costantino, E. Mazzon, and A. P. Caputi, “Regulation of Prostaglandin Production in Carrageenan-Induced Pleurisy Melatonin,” <i>Journal of Pineal Research</i> 27, no. 1 (1999): 9-14, https://doi.org/10.1111/j.1600-079X.1999.tb00591.x.</p><p>The above article, published online on 30 January 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, the sample shown in Figure 3A has been identified as being used in a different scientific context in another article from the same author group, which was submitted concurrently. The data provided by the corresponding author upon request was insufficient to address the concerns. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70011","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749264","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: Protective Effect of Melatonin in a Non-Septic Shock Model Induced by Zymosan in the Rat","authors":"","doi":"10.1111/jpi.70013","DOIUrl":"https://doi.org/10.1111/jpi.70013","url":null,"abstract":"<p><b>RETRACTION</b>: S. Cuzzocrea, B. Zingarelli, G. Costantino, and A. R. Caputi, “Protective Effect of Melatonin in a Non-Septic Shock Model Induced by Zymosan in the Rat,” <i>Journal of Pineal Research</i> 25, no. 1 (1998): 24–33, https://doi.org/10.1111/j.1600-079X.1998.tb00382.x.</p><p>The above article, published online on 30 January 2007 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, there is evidence of image duplication between Figures 6A and 6C, indicating that the same biological sample has been utilized to represent two distinct experimental conditions. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70013","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749263","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: Melatonin Prevents Lipopolysaccharide-induced Hyporeactivity in Rat","authors":"","doi":"10.1111/jpi.70012","DOIUrl":"https://doi.org/10.1111/jpi.70012","url":null,"abstract":"<p><b>RETRACTION:</b> R. D'Emmanuele Di Villa Bianca, S. Marzocco, R. Di Paola, G. Autore, A. Pinto, S. Cuzzocrea, and R. Sorrentino, “Melatonin Prevents Lipopolysaccharide-induced Hyporeactivity in Rat,” <i>Journal of Pineal Research</i> 36, no. 3 (2004): 146-154, https://doi.org/10.1046/j.1600-079X.2003.00111.x.</p><p>The above article, published online on 8 March 2004 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini; and John Wiley &amp; Sons Ltd. The retraction has been agreed due to concerns raised by third parties on the data presented in the article. Specifically, there is evidence of image duplication between Figures 6A and 8A, indicating that the same biological sample has been utilized to represent two distinct experimental conditions. The article is retracted as the editors have lost trust in the accuracy and integrity of the overall body of data presented in the article and consider its conclusions invalid.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70012","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142749261","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 Activity of Melatonin Combinations and Melatonin-Based Hybrid Molecules in Neurodegenerative Diseases","authors":"Francesca Galvani,&nbsp;Mariarosaria Cammarota,&nbsp;Federica Vacondio,&nbsp;Silvia Rivara,&nbsp;Francesca Boscia","doi":"10.1111/jpi.70008","DOIUrl":"https://doi.org/10.1111/jpi.70008","url":null,"abstract":"<p>The identification of protective agents for the treatment of neurodegenerative diseases is the mainstay therapeutic goal to modify the disease course and arrest the irreversible disability progression. Pharmacological therapies synergistically targeting multiple pathogenic pathways, including oxidative stress, mitochondrial dysfunction, and inflammation, are prime candidates for neuroprotection. Combination or synergistic therapy with melatonin, whose decline correlates with altered sleep/wake cycle and impaired glymphatic “waste clearance” system in neurodegenerative diseases, has a great therapeutic potential to treat inflammatory neurodegenerative states. Despite the protective outcomes observed in preclinical studies, mild or poor outcomes were observed in clinical settings, suggesting that melatonin combinations promoting synergistic actions at appropriate doses might be more suitable to treat multifactorial neurodegenerative disorders. In this review, we first summarize the key melatonin actions and pathways contributing to cell protection and its therapeutic implication in Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). We remark the major controversies in the field, mostly generated by the lack of a common consensus for the optimal dosing, molecular targets, and toxicity. Then, we review the literature investigating the efficacy of melatonin combinations with approved or investigational neuroprotective agents and of melatonin-containing hybrid molecules, both in vitro and in animal models of AD, PD, and MS, as well as the efficacy of add-on melatonin in clinical settings. We highlight the rationale for such melatonin combinations with a focus on the comparison with single-agent treatment and on the assays in which an additive or a synergistic effect has been achieved. We conclude that a better characterization of the mechanisms underlying such melatonin synergistic actions under neuroinflammation at appropriate doses needs to be tackled to advance successful clinical translation of neuroprotective melatonin combination therapies or melatonin-based hybrid molecules.</p>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/jpi.70008","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142708051","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":"Heat Treatment of Saliva to Reduce Infectious Disease Contamination Does Not Impact the Analysis of Melatonin by Radioimmunoassay","authors":"Mark D. Salkeld,&nbsp;David J. Kennaway","doi":"10.1111/jpi.70009","DOIUrl":"10.1111/jpi.70009","url":null,"abstract":"<div>\u0000 \u0000 <p>The determination of melatonin levels in saliva represents one of the key methods for assessing the timing of the central circadian clock in humans, both in research and clinical settings. Melatonin levels in saliva are typically determined in a laboratory setting by RIA or enzyme-linked immunosorbent assay and the emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presented a serious challenge to the routine, safe assessment of melatonin in saliva samples. However, SARS-CoV-2 present in biological fluids can be inactivated by exposure to temperatures of at least 55–60°C for 30 min and the aim of this study was to assess the validity of applying a pretreatment heating step to saliva samples being prepared for melatonin determination using the Novolytix Radioimmunoassay (RK-DSM2). 40 archived saliva samples collected under a Dim Light Melatonin Onset sampling protocol were thawed and aliquoted into three identical groups—Controls (no pretreatment), 56°C pre-assay heat-treatment (30 min), and 70°C pre-assay heat-treatment (30 min). Melatonin concentrations in samples that were heated to 56°C for 30 min before assaying showed close agreement with the untreated controls, with the Pearson's correlation coefficient between the two sets of samples of 0.99 (<i>p</i> &lt; 0.0001) and the slope of the Deming regression analysis close to 1.0 (<i>Y</i> = 1.04<i>X</i> + 0.168). When saliva samples were pretreated to 70°C for 30 min before assaying, the subsequent melatonin determinations were still strongly correlated with the untreated controls (Pearsons correlation coefficient = 0.97 (<i>p</i> &lt; 0.0001), however melatonin concentrations were consistently overestimated when compared to the untreated controls with Deming regression slope of <i>Y</i> = 1.26<i>X</i> + 0.241. These results indicate that a 56°C pretreatment step is suitable for inclusion in standard operating protocols for melatonin determinations using the Novolytix RIA, as a way of effectively minimizing the potential for accidental pathogen exposure while handling saliva samples.</p>\u0000 </div>","PeriodicalId":198,"journal":{"name":"Journal of Pineal Research","volume":"76 8","pages":""},"PeriodicalIF":8.3,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142674484","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 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}