Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie最新文献

{"title":"Astaxanthin protects fludrocortisone acetate-induced cardiac injury by attenuating oxidative stress, fibrosis, and inflammation through TGF-β/Smad signaling pathway.","authors":"Manoneeta Sarker, Nowreen Chowdhury, Anika Tabassum Bristy, Tushar Emran, Reatul Karim, Rezwana Ahmed, Md Mostaid Shaki, Shazid Md Sharkar, G M Sayedur Rahman, Hasan Mahmud Reza","doi":"10.1016/j.biopha.2024.117703","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117703","url":null,"abstract":"<p><p>Hypertensive rats serve as a good experimental model for studying the pathophysiology of cardiac hypertrophy and remodeling leading to heart failure. In this study, we aimed to analyze the effect of astaxanthin and possible mechanisms involved in alleviating oxidative stress, fibrosis and inflammation that triggers cardiac remodeling using male uninephrectomized Long Evans rats. Cardiac hypertrophy and hypertension were induced in rats termed as 'FCA-Salt rats' by an oral administration of fludrocortisone acetate (FCA) and 1 % NaCl in drinking water. Biochemical assays showed that FCA-Salt rats exhibited an upregulation of oxidative stress markers AOPP, MDA and downregulation of NO in heart and kidney, which was reversed by astaxanthin treatment. Astaxanthin further regularized the reduced activities of antioxidant enzymes GSH, SOD and CAT in these tissues. ELISA revealed that astaxanthin significantly reduced the inflammatory response by reducing the elevated levels of IL-1β, IL-17a, and TNF-α and pro-fibrotic marker TGF-β1 in plasma. Real-time qPCR depicted an upregulation of TNF-α, IL-1β, IL-6, IL-17A as well as signaling molecules TGF-β1, Smad2 and Smad3 in heart of FCA-Salt rats, which was reduced significantly by astaxanthin. Sirius red staining showed that the cardiac and renal fibrosis was significantly improved by astaxanthin treatment. Together, our results suggest that astaxanthin treatment is beneficial in protecting cardio-renal damage in hypertension through TGF-β/Smad signaling pathway, hence, this molecule may be considered for the maintenance of cardio-renal health.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117703"},"PeriodicalIF":0.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Discovery of amino acid-conjugated dimethylcardamonin analogues as potent anti-cervical cancer agents on SiHa cells targeting p53 signalling pathway.","authors":"Nopawit Khamto, Kraikrit Utama, Pornthip Chawapun, Sadanon Siriphong, Suriya Tateing, Sarocha Duangdesh, Padchanee Sangthong, Ni-Orn Chomsri, Puttinan Meepowpan","doi":"10.1016/j.biopha.2024.117705","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117705","url":null,"abstract":"<p><p>DMC (1) is a phytochemical found in the seeds of Syzygium nervosum, exhibiting anticancer activity in various cells through multiple pathways. Herein, the bioactivity of DMC (1) was enhanced by chemical modification through esterification, attaching fatty acid and amino acid moieties to yield 27 semi-synthetic derivatives. These compounds were evaluated for their in vitro cytotoxicity against three main types of cervical cancer cells, including SiHa, HeLa, and C-33A. As a result, the amino acid DMC derivative, 4´-(L-tyrosinyloxy)-DMC (7j), exhibited potent cytotoxicity against SiHa cells, which was approximately two-fold greater than that of 1. Further investigation into the mechanism of action of 7j was conducted, revealing its ability to induce cell cycle arrest and apoptosis. Gene expression analysis showed the downregulation of CDK2 and upregulation of the BAX/BCL2 ratio. Atomistic insight was studied on HPV 16 E6 via molecular dynamics simulation, revealing key interactions between tyrosinyl portion and C51 residue.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117705"},"PeriodicalIF":0.0,"publicationDate":"2024-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142718043","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Butyrate modulates gut microbiota and anti-inflammatory response in attenuating cisplatin-induced kidney injury.","authors":"Wen-Jung Chen, Yng-Tay Chen, Jiunn-Liang Ko, Jian-Yuan Chen, Jun-Yao Zheng, Jiunn-Wang Liao, Chu-Chyn Ou","doi":"10.1016/j.biopha.2024.117689","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117689","url":null,"abstract":"<p><p>In our previous research, we reported that administering probiotics Lactobacillus reuteri and Clostridium butyricum (LCs) before cisplatin treatment effectively modifies structures of the gut microbiota and restore ecological balance and significantly increases butyrate levels, a process closely associated with reducing cisplatin-induced nephrotoxicity. This study aims to investigate further whether the elevation of metabolite butyrate in the gut, promoted by probiotics LCs, can effectively mitigate the nephrotoxic effects of cisplatin and the progression of renal senescence in rats. Results show that butyrate administration significantly improved kidney function and decreased renal fibrosis in a dose-dependent manner compared to the cisplatin group. Its effects were associated with reductions in inflammatory responses, evidenced by decreased levels of key inflammatory markers, including KIM-1, MPO, NOX2, F4/80, and TGF-β1, alongside increased production of the anti-inflammatory cytokine IL-10. Furthermore, the butyrate intervention ameliorated cisplatin-induced gut microbiota dysbiosis, preserving the structure and diversity of healthy microbial communities. Specifically, we observed a decrease in the abundance of Escherichia_Shigella and Blautia, alongside an increase in the abundance of the butyrate-producing genus Roseburia. Notably, Escherichia_Shigella exhibited a positive correlation with the pro-inflammatory factor MPO, while displaying a negative correlation with the anti-inflammatory cytokine IL-10. Butyrate also attenuated the cisplatin-induced expression of senescence markers p21 and p16 in kidney tissue. It alleviated the cisplatin-increased senescence-associated beta-galactosidase activity and reactive oxygen species production in SV40 MES-13 cells. These results indicate that butyrate, derived from the gut microbiota, may exert a protective effect against cisplatin-induced kidney damage by regulating microbiota balance and anti-inflammatory effects.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117689"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711837","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hydrocephalus: An update on latest progress in pathophysiological and therapeutic research.","authors":"Faheem Anwar, Kuo Zhang, Changcheng Sun, Meijun Pang, Wanqi Zhou, Haodong Li, Runnan He, Xiuyun Liu, Dong Ming","doi":"10.1016/j.biopha.2024.117702","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117702","url":null,"abstract":"<p><p>Hydrocephalus is a severe and life-threatening disease associated with the imbalance of CSF dynamics and affects millions globally at any age, including infants. One cause of pathology that is wide-ranging is genetic mutations to post-traumatic injury. The most effective current pharmacological treatments provide only symptomatic relief and do not address the underlying pathology. At the same time, surgical procedures such as VP shunts performed in lower-income countries are often poorly tolerated due to insufficient diagnostic resources and suboptimal outcomes partially attributable to inferior materials. These problems are compounded by an overall lack of funding that keeps high-quality medical devices out of reach for all but the most developed countries and even among those states. There is a massive variance in treatment effectiveness. This review indicates the necessity for innovative and low-cost, accessible treatment strategies to close these gaps, focusing on current advances in novel therapies, including Pharmacological, gene therapy, and nano-based technologies, which are currently at different stages of clinical trial phases. This review provides an overview of pathophysiology, current treatments, and promising new therapeutic strategies for hydrocephalus.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117702"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711838","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A new perspective on targeting pulmonary arterial hypertension: Programmed cell death pathways (Autophagy, Pyroptosis, Ferroptosis).","authors":"Qingliang Ge, Tianqing Zhang, Jiangbiao Yu, Xuelin Lu, Sijie Xiao, Ting Zhang, Tao Qing, Zhenni Xiao, Liuting Zeng, Li Luo","doi":"10.1016/j.biopha.2024.117706","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117706","url":null,"abstract":"<p><p>Pulmonary arterial hypertension (PAH) is a severe cardiovascular disease characterized by elevated pulmonary vascular resistance, progressive increases in pulmonary artery pressures, ultimately leading to right-sided heart failure, and potentially mortality. Pulmonary vascular remodeling is pivotal in PAH onset and progression. While targeted drug therapies have notably ameliorated PAH prognosis, current medications primarily focus on vascular vasodilation, with limited ability to reverse pulmonary vascular remodeling fundamentally, resulting in suboptimal patient prognoses. Cellular death in pulmonary vasculature, once thought to be confined to apoptosis and necrosis, has evolved with the identification of pyroptosis, autophagy, and ferroptosis, revealing their association with vascular injury in PAH. These novel forms of regulated cellular death impact reactive oxygen species (ROS) generation, calcium stress, and inflammatory cascades, leading to pulmonary vascular cell loss, exacerbating vascular injury, and mediating adverse remodeling, inflammation, immune anomalies, and current emerging mechanisms (such as endothelial-mesenchymal transition, abnormal energy metabolism, and epigenetic regulation) in the pathogenesis of PAH. This review comprehensively delineates the roles of autophagy, pyroptosis, and ferroptosis in PAH, elucidating recent advances in their involvement and regulation of vascular injury. It juxtaposes their distinct functions in PAH and discusses the interplay of these programmed cell deaths in pulmonary vascular injury, highlighting the benefits of combined targeted therapies in mitigating pulmonary arterial hypertension-induced vascular injury, providing novel insights into targeted treatments for pulmonary arterial hypertension.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117706"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711819","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TNF signaling mediates lipopolysaccharide-induced lung epithelial progenitor cell responses in mouse lung organoids.","authors":"Dan Li, Rosa K Kortekaas, Kelly B I Douglas, Wanda Douwenga, Ulrich L M Eisel, Barbro N Melgert, Reinoud Gosens, Martina Schmidt","doi":"10.1016/j.biopha.2024.117704","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117704","url":null,"abstract":"<p><p>Bacterial respiratory infections are a major global health concern, often leading to lung injury and triggering lung repair mechanisms. Endogenous epithelial progenitor cells are crucial in this repair, yet the mechanisms remain poorly understood. This study investigates the response of lung epithelial progenitor cells to injury induced by lipopolysaccharide (LPS), a component of gram-negative bacteria, focusing on their regulation during lung repair. Lung epithelial cells (CD31^-CD45^-Epcam⁺) from wild-type and tumor necrosis factor (TNF) receptor 1/2 knock-out mice were co-cultured with wild-type fibroblasts. Organoid numbers and size were measured after 14 days of exposure to 100 ng/mL LPS. Immunofluorescence was used to assess differentiation (after 14 days), RNA sequencing analyzed gene expression changes (after 72 hours), and MTS assay assessed proliferative effects of LPS on individual cell types (after 24 hours). LPS treatment increased the number and size of wild-type lung organoids and promoted alveolar differentiation, indicated by more SPC⁺ organoids. RNA sequencing revealed upregulation of inflammatory and fibrosis-related markers, including Cxcl3, Cxcl5, Ccl20, Mmp13, and Il33, and enrichment of TNF-α signaling and epithelial-mesenchymal transition pathways. TNF receptor 1 deficiency inhibited LPS-induced progenitor cell activation and organoid growth. In conclusion, LPS enhances lung epithelial progenitor cell proliferation and differentiation via TNF receptor 1 signaling, highlighting potential therapeutic targets for bacterial lung injury.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117704"},"PeriodicalIF":0.0,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142711840","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recombinant soluble type I interferon receptor exerts antiviral activity by inducing proteins related to autophagy.","authors":"Pablo Aliaga-Gaspar, Isabel Brichette-Mieg, MdM Fernández-Arjona, José Luis Rodríguez-Bada, Yolanda López-Moreno, Pedro Serrano-Castro, Oscar Fernández-Fernández, Nicolás Lundahl Ciano-Petersen, Begoña Oliver-Martos","doi":"10.1016/j.biopha.2024.117678","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117678","url":null,"abstract":"<p><p>The soluble type I IFN receptor (sIFNAR2) is produced by alternative splicing and is present in body fluids. Although it can modulate IFN-ß activity, its biological role remains unknown.</p><p><strong>Methods: </strong>An in-silico study was conducted to compare the structure of recombinant human soluble IFNAR2 (r-sIFNAR2) with its native form. The antiviral activity of r-sIFNAR2, produced in BL21-bacteria and CHO cells, was tested using a cytopathic effect assay including appropriate controls. Viability and toxicity were assessed by MTT assays. Proteomic analysis using mass spectrometry was conducted in the A549/EMCV bioassay to elucidate the mechanism of action, and then it was validated by Western blot.</p><p><strong>Results: </strong>The BL21-sIFNAR2 had a sequence identity of 83.6 % with the native form, showing variations only in terminal regions. BL21-sIFNAR2 and CHO-sIFNAR2 showed significantly higher percentage of cell viability compared to the viral control, similar to IFN-ß. Cell viability with BL21-sIFNAR2 was comparable to the cell control across all tested concentrations. Proteomic analysis revealed an up regulation of pathways related with autophagy (macroautophagy, autophagy, pexophagy, and mitophagy) with an SQSTM1 overexpression that was then confirmed by Western Blot, especially after virus infection. However, pathways related to interferon signaling, and antiviral mechanisms mediated by IFN-stimulated genes were down-regulated.</p><p><strong>Conclusion: </strong>r-sIFNAR2 exhibits significant antiviral activity regardless of the expression system used for its production and good safety profile, suggesting its use as a potential antiviral drug. Proteins related to autophagy are involved in the protection from the virus. This study highlights the biological relevance of soluble cytokine receptors as effectors so far overlooked.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117678"},"PeriodicalIF":0.0,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693990","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cellucalst enzyme-assisted extraction of Sargassum horneri enhances the immunomodulation by regulating TLR4/MyD88/NF-kB pathway in murine splenocytes with or without Concanavalin A.","authors":"Jiwon Yang, Hyo Jin Kim, Kalahe Hewage Iresha Nadeeka Madushani Herath, Youngheun Jee","doi":"10.1016/j.biopha.2024.117673","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117673","url":null,"abstract":"<p><p>Sargassum horneri (S. horneri) is an edible species of large brown algae inhabiting along the coasts of northeastern Asia. The study focuses on the impact of celluclast enzyme extract of S. hoeneri (SHC) on various immune cell populations in splenocytes including granulocytes, macrophages, dendritic cells, and T lymphocytes. SHC alone increased the population of granulocytes and macrophages and the secretion of M1 macrophage-derived cytokines (TNF-α, IL-22), and M2 macrophage-derived cytokines (IL-4, IL-10). Interestingly, however, SHC suppressed the concanavalin A (Con A)-expanded populations of macrophages, dendritic cells, granulocytes, T and B cells, and Con A-promoted secretion of M1-macrophage derived cytokines (IFN-γ, IL-1β, TNF-α, IL-17, IL-22) and M2-macrophage derived cytokines (IL-4, IL-10, IL-13, TGF-β). SHC further restrained the Th1, Th2, and Th17 cell responses through attenuating the expression of respective transcription factors T-bet, Gata3, and Rorγt. The anti-inflammatory property of SHC is highlighted through its influence on cytokine production, particularly in the NF-κB pathway, and the attenuation of Toll-like receptor (TLR) signaling. The results reveal that SHC acts as both an immunostimulator and an inhibitor of hyperimmune reactions, showcasing its potential therapeutic applications in conditions involving dysregulated immune responses such as autoimmune diseases and inflammatory disorders. This positions SHC as a promising candidate for the development of functional ingredients with diverse applications encompassing the realms of food, pharmaceuticals, and cosmetics.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117673"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Population pharmacokinetics of unfractionated heparin and multivariable analysis of activated clotting time in patients undergoing radiofrequency ablation of atrial fibrillation.","authors":"Celine Konecki, François Lesaffre, Sophie Guillou, Catherine Feliu, Florine Dubuisson, Moad Labdaoui, Laurent Faroux, Zoubir Djerada","doi":"10.1016/j.biopha.2024.117700","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117700","url":null,"abstract":"<p><strong>Introduction: </strong>Atrial fibrillation (AF) increases cardiovascular morbidity and mortality. To reduce thrombosis and bleeding risks, and due to high variability of unfractionated heparin (UFH) effect, activated clotting time (ACT) is used during radiofrequency catheter ablation (RFCA) of AF to guide UFH dose. This study aimed to develop a population PK-PD model and perform multivariable analysis in order to identify the most significant covariates associated with interindividual variability of UFH.</p><p><strong>Methods: </strong>Electronic medical records from 668 patients undergoing RFCA were analyzed, including relevant covariates. The relationship between UFH dose and ACT and the impact of the main covariates were characterized using a mixed-effect PK-PD model. Multivariable analysis was then used to identify predictors of ACT 15 minutes after UFH administration (ACT15).</p><p><strong>Results: </strong>A two-compartment PK model with linear elimination and a direct Emax PD model with a baseline and sigmoidicity best described the observed ACT values. Pretreatment with dabigatran, warfarin, or fluindione significantly influenced baseline ACT. Pretreatment with vitamin K antagonists or low molecular weight heparin explained Emax variability. The multivariable model identified baseline ACT, initial UFH dose, and previous anticoagulant as the main predictors of ACT15. Model evaluation through resampling and external validation showed accurate ACT15 predictions.</p><p><strong>Conclusion: </strong>This study presents the first population PK-PD model characterizing the relationship between UFH doses and ACT during RFCA, along with multivariable analysis. Additionally, predictive calculators for ACT15 and UFH dose based on patient and procedural characteristics were developed, enhancing personalized anticoagulation management during RFCA.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117700"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690051","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Prenatal THC exposure drives sex-specific alterations in spatial memory and hippocampal excitatory/inhibitory balance in adolescent rats.","authors":"Valentina Castelli, Gianluca Lavanco, Giuseppe Tringali, Cesare D'Amico, Salvatore Feo, Martina Di Bartolomeo, Claudio D'Addario, Martin Kuchar, Anna Brancato, Carla Cannizzaro","doi":"10.1016/j.biopha.2024.117699","DOIUrl":"https://doi.org/10.1016/j.biopha.2024.117699","url":null,"abstract":"<p><p>The interaction between the main psychotropic ingredient of Cannabis, Δ⁹- tetrahydrocannabinol (THC), with the endogenous cannabinoid system (ECS) is a critical and underrated issue that deserves utmost attention. The ECS, indeed, contributes to the formation and regulation of excitatory and inhibitory (E/I) neuronal networks that in the hippocampus underly spatial memory. This study explored sex-specific consequences of prenatal exposure to THC in hippocampus-dependent memory and the underlying cellular and molecular contributors of synaptic plasticity and E/I homeostasis. Sprague Dawley dams were exposed to THC (2 mg/kg) or vehicle, from gestational day 5-20. The adolescent progeny of both sexes was tested for: spatial memory retrieval and flexibility in the Barnes Maze; mRNA expression of relevant players of hippocampal synaptic plasticity; density of cholecystokinin-positive basket cells (CCK+BCs) - a major subtype of hippocampal inhibitory interneurons; mRNA expression of the excitatory and inhibitory synaptic proteins neuroligins (Nlgns), as a proxy of synaptic efficiency. Our results show a sex-specific disruption in spatial memory retrieval and flexibility, a male-specific decrease in CCK+BCs density and increase in the expression of markers of neuroplasticity, and consistent changes in the expression of Nlgn-1 and 3 isoforms. Despite a delay in memory retrieval, flexibility of memory was spared in prenatally-THC-exposed female offspring as well as most of the markers of neuroplasticity; a sex-specific increase in CCK+BCs density, and a consistent expression of Nlgn-3 was observed. The current results highlight a major vulnerability to prenatal exposure to THC on memory processing in the male progeny, and sex-specific alterations in the E/I balance and synaptic plasticity.</p>","PeriodicalId":93904,"journal":{"name":"Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie","volume":"181 ","pages":"117699"},"PeriodicalIF":0.0,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690080","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}