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The Suok 'ropewalking' test of rodent anxiety and sensorimotor disintegration: А 20-year summary of its application in neuroscience research

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Behavioural brain research 2025年 493卷 115677页

作者： Vyacheslav D Riga Alisa E Makhortykh David S Galstyan Murilo S de Abreu Allan V Kalueff Neurobiology Program Scientific Center for Genetics and Life Sciences Sirius University of Science and Technology Federal Territory Sirius Sochi Russia. Almazov National Medical Research Centre Petersburg Russia Institute of Translational Biomedicine St. Petersburg State University Petersburg Russia. Graduate Program in Health Sciences Federal University of Health Sciences of Porto Alegre Porto Alegre Brazil Western Caspian University Baku Azerbaijan. Electronic address: abreu_murilo@***. Department of Biosciences and Bioinformatics School of Science Xi'an Jiaotong-Liverpool University Suzhou China Suzhou Key Municipal Laboratory of Neurobiology and Cell Signaling School of Science Xi'an Jiaotong-Liverpool University Suzhou China. Electronic address: avkalueff@***.

The Suok (ropewalking) test has been developed in 2004 to simultaneously assess rodent locomotor activity, anxiety-like behavior, sensorimotor disintegration, and their interplay. Over the last 20 years, this 'hybrid' test has been used in rat and mouse neurobehavioral research by various laboratories globally. Here, we provide a detailed overview of the Suok test, its past and present uses, methodological strengths, limitations, the existing problems, potential future modifications and practical applications. We also discuss the implications of results obtained in this test for improving our understanding of brain pathogenesis and the development of therapies for anxiety, vestibular disorders, sensorimotor disintegration and its stress-induced subtype. Finally, we suggest novel potential avenues for adapting this behavioral paradigm to the current needs and challenges of rodent preclinical neuroscience and drug discovery research.

关键词： Anxiety Behavioral assay Rodents Sensorimotor disintegration Stress

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Development and Evaluation of a Support Intervention for Families after Sudden Cardiac Death

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Heart, Lung and Circulation 2024年 33卷 S120-S120页

作者： L. Yeates A. Baker K. Gardner J. Do N. Stewart L. Catto F. Leslie C. Semsarian B. Gray A. McEwen L. Adlard J. Ingles Genomics and Inherited Disease Program Garvan Institute of Medical Research Darlinghurst NSW Australia Agnes Ginges Centre for Molecular Cardiology Centenary Institute The University of Sydney Sydney NSW Australia Sydney Medical School Faculty of Medicine and Health The University of Sydney Sydney NSW Australia Department of Cardiology Royal Prince Alfred Hospital Sydney NSW Australia Academic Unit of General Practice ANU Medical School Australian National University Canberra ACT Australia National Centre for Epidemiology and Population College of Health and Medicine Australian National University Canberra ACT Australia Graduate School of Health University of Technology Sydney Sydney NSW Australia Faculty of Medicine and Health University of New South Wales Sydney NSW Australia

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CNSC-37. ROLE OF PGE2-REGULATED NEUROINFLAMMATION IN CONSTRUCTING NEURON-NK-GLIOMA CIRCUIT FOR GLIOBLASTOMA

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Neuro-Oncology 2024年第SUPPLEMENT_8期26卷 viii49–viii49页

作者： Chen, Hsien-Chung Chang, Wen-Chang Hsu, Tsung-Yi Department of Neurosurgery Shuang Ho Hospital Taipei Medical University Taipei Taiwan Ph.D. Program in Medical Neuroscience College of Medical Science and Technology Taipei Medical University and National Health Research Institutes Taipei Taiwan TMU Research Center of Neuroscience Taipei Medical University Taipei Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei Taiwan TMU Research Center for Drug Discovery Taipei Medical University Taipei Taiwan

Glioblastoma (GBM), known for its aggressive nature and poor prognosis, frequently recurs and resists standard treatments such as temozolomide (TMZ). This resistance is partly due to complex interactions within the tumor microenvironment, particularly involving neuronal excitation. Recent insights suggest that neuronal activity, through mechanisms like neurogliomal synapses, not only promotes glioma cell proliferation but also contributes to the chemoresistance observed in recurrent tumors. Our focus is on Prostaglandin E2 (PGE2), a mediator that regulates neuronal excitation, and its role in the recurrence and resistance of GBM. We discovered that PGE2 upregulates synaptic proteins and alters neurotransmitter profiles, enhancing tumor cell survival and resistance to TMZ. Specifically, increased levels of neurotransmitters such as glutamine and asparagine were observed in PGE2-rich environments, correlating with heightened chemoresistance and tumor recurrence. Co-culture experiments further demonstrated that PGE2-treated neuronal cells could induce resistance in adjacent GBM cells. These findings highlight the potential of targeting PGE2 pathways as a therapeutic strategy. A significant advancement in our study was the development and application of compound #038, a novel celecoxib derivative designed to cross the blood-brain barrier (BBB). This compound demonstrated enhanced efficacy in inhibiting GBM growth and improving survival rates in mouse models, indicating its potential as an effective therapeutic agent against GBM.

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Family and caregiver perspectives on gene therapy for Rett syndrome

Rare. Open Research in Rare Diseases

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Rare. Open Research in Rare Diseases 2024年 2卷 100045-100045页

作者： Ramsey, Keri LaFleur, Madison Robinson, Kiana Borgstrom, Mark Ryan, Ashley Narayanan, Vinodh Schaibley, Valerie Genetic Counseling Graduate Program University of Arizona Health Sciences Tucson AZ USA Department of Cellular and Molecular Medicine University of Arizona College of Medicine Tucson AZ USA Center for Rare Childhood Disorders Translational Genomics Research Institute Phoenix AZ USA Translational Genomics Research Institute Phoenix AZ USA Natera Inc. San Carlos CA USA University Information Technology Services University of Arizona Tucson AZ USA

AbstractIntroductionRett syndrome (RTT) is a neurodevelopmental disorder that primarily affects females and can result in cognitive impairment, seizures, spasticity, breathing problems, gastrointestinal issues, motor impairment, and behavioral concerns. Gene therapy may be a potential treatment in the future as clinical trials are underway. AimThis study evaluates the attitudes and opinions of family members and caregivers of patients with RTT towards gene therapy using a mixed-method approach. MethodsSixty-six caregivers of individuals with RTT completed an online survey asking about their previous experience in research and questions about their understanding of gene therapy, their expectations, as well as their hopes and concerns for treating RTT. Ten respondents also participated in online focus groups, which were evaluated using thematic analysis. ResultsOverall, most participants (95.5 %) had heard about gene therapy. More than half of the respondents (68.2 %) reported being somewhat knowledgeable about gene therapy, and 18.2 % reported no understanding of gene therapy. When asked the highest level of risk they would accept when enrolling the individual with Rett syndrome in a gene therapy clinical trial, 47.7 % stated they would accept a low risk, and 7.7 % indicated they would accept a high risk. In the focus groups, individuals discussed barriers to gene therapy, their hopes and concerns regarding gene therapy treatment, and how they would like to receive information about future research and therapies. Participants had concerns about possible side effects of gene therapy, including physical and mental harm, a potential decrease in quality of life, whether individuals with RTT would want to “change who they are,” and the irreversibility of the treatment. ConclusionAlthough most participants have heard about gene therapy, many caregivers would only accept a low risk when considering gene therapy for the individual with RTT. This could be in part due to conce

关键词： Rett syndrome Gene therapy Risk Caregiver

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Microstructural and proteomic analysis to investigate the effectiveness of papaya leaf as a tenderizer of beef and goat's meat

Microstructural and proteomic analysis to investigate the ef...

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International Conference on Food Science and technology 2018, ICFST 2018

作者： Kartika, A.I. Kusuma, H.S. Darmawati, S. Tanjung, D.S. Molecular Biology Laboratory Medical Laboratory Technology D4 Health and Nursing Faculty Universitas Muhammadiyah Semarang Indonesia Nutrition Laboratory Health and Nursing Faculty Universitas Muhammadiyah Semarang Indonesia Post Graduate Program in Biotechnology School of Postgraduate Universitas Gadjah Mada St. Teknika Utara Barek Caturtunggal Daerah Istimewa Yogyakarta55281 Indonesia

Meat quality for the community is determined by the level of tenderizer. The process of meat tenderization could be done by giving papain enzymes derived from papaya fruit or leaves. Meat with the administration of papain enzymes can be analyzed based on protein profiles to see protein and microstructural integrity to see the texture of meat. The research sample was 20 g of beef and goat's meat with the treatment using the enzyme papain derived from papaya leaves. Time variation of enzyme administration 1 h, 2 h, 4 h, and 8 h, as well as variations in the weight of crude papain extract from papaya leaves as much as 10 g, 15 g, and 20 g. Analysis of protein concentration using Bradford and Kjeldhal methods, and protein profiles using the SDS PAGE method, and microstructural analysis using SEM. The concentration of meat protein with the treatment of crude extract of papaya leaves decreased compared to control meat. Based on protein profile analysis showed that meat given the enzyme papain from papaya leaves experienced protein band loss at a size of 225 kDa, 150 kDa, 96 kDa, 86 kDa. Microstructural analysis showed that beef and goat's meat treated with damage to collagen fibers, collagen fibers did not stick with muscle fibers, and the arrangement was irregular, in addition, there was a distance between muscle fibers. © 2019 Published under licence by IOP Publishing Ltd.

关键词： Textures

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SRT1720 as an SIRT1 Activator for Alleviating Paraquat-Induced Models of Parkinson's Disease

SSRN

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SSRN 2022年

作者： Chao, Chih-Chang Huang, Chuen-Lin Cheng, Jing-Jy Chiou, Chun-Tang Lee, I-Jung Yang, Ying-Chen Hsu, Ting-Huang Yei, Chan Lin, Pei-Yin Cheng, Jih-Jung Huang, Nai-Kuei Institute of Neuroscience National Chengchi University Taipei Taiwan Medical Research Center Cardinal Tien Hospital Hsintien New Taipei City Taiwan Graduate Institute of Physiology Department of Physiology and Biophysics National Defense Medical Center Taipei114 Taiwan National Research Institute of Chinese Medicine Ministry of Health and Welfare Taipei112 Taiwan Institute of Biophotonics National Yang-Ming University Taipei112 Taiwan Herbal Medicine Department Yokohama University of Pharmacy Yokohama Japan Department of Biotechnology and Animal Science National Ilan University Ilan Taiwan School of Pharmaceutical Sciences National Yang-Ming Chiao Tung University Taipei Taiwan Ph.D. Program for Neural Regenerative Medicine College of Medical Science and Technology Taipei Medical University Taipei11031 Taiwan Graduate Institute of Medical Sciences College of Medicine Taipei Medical University Taipei11031 Taiwan

Epidemiological studies have linked herbicides and Parkinson’s disease (PD), with the strongest associations resulting from long exposure durations. Paraquat (PQ), an herbicide, induces PD-like syndromes and has widely been accepted as a PD mimetic. Currently, there is still no cure to prevent the progression of PD, and the search for effective therapeutic ways is urgent. Recently, the impairing activity of sirtuins (SIRTs), such as SIRT1, may correlate with PD etiology. However, the nonspecificity of SIRT1 agonists has made the protective mechanisms against PD unclear and hampered the therapeutic application of SIRT1. Thus, this study investigated the protective mechanism and therapeutic potential of SRT1720, a more specific agonist for SIRT1, in alleviating the toxicity of PQ-induced cellular and animal models of PD. Here we show that SRT1720 alleviates PQ-induced toxicity in cell and animal models. Genetic silencing and pharmacological inhibition of SIRT1 attenuated SRT1720’s protection against PQ-induced toxicity. Moreover, SRT1720 not only attenuated PQ-induced increased oxidative stress and mitochondrial free radical formations but also decreased mitochondrial membrane potential. Furthermore, SRT1720 reversed PQ-induced decreased PGC-1α levels and mitochondrial biogenesis. Although PQ and SRT1720 elevated NRF2 and antioxidative enzyme levels, only PQ decreased antioxidative enzyme activity but not SRT1720. NRF2 and PGC-1α silencing attenuated SRT1720 protection against PQ-induced toxicity. SRT1720 targeted SIRT1 and activated downstream PGC-1a and NRF2 signalings to prevent PQ-induced toxicity involving oxidative stress and mitochondrial dysfunction. Thus, SRT1720 might have therapeutic potential in preventing PD. © 2022, The Authors. All rights reserved.

关键词： Mitochondria

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AB0988 TELOMERE LENGTH ASSOCIATION WITH CLINICAL CHARACTERISTICS AND COGNITION IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS: A CROSS-SECTIONAL STUDY

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Annals of the Rheumatic Diseases 2024年 83卷 1810-1810页

作者： A.C. Faria Moreira Gomes Tavares M.A. Camargos Bicalho C. Ruas Freire Santos J. Martins Amaral I.C. Bolaños Burgos D. Valadão Freitas Rosa D. Marques De Miranda M.A. Romano-Silva G.A. Ferreira A.M. Kakehasi Federal University of Minas Gerais Post Graduate Program in Sciences Applied to Adult Health Care Belo Horizonte Brazil Federal University of Minas Gerais Clinics Hospital Belo Horizonte Brazil Federal University of Minas Gerais Belo Horizonte Brazil Federal University of Minas Gerais National Institute of Science and Technology in Molecular Medicine Belo Horizonte Brazil Federal University of Minas Gerais Neurotec R National Institute of Science and Technology (INCT-Neurotec R) Belo Horizonte Brazil federal University of Minas Gerais Neurotec R National Institute of Science and Technology (INCT-Neurotec R) Belo Horizonte Brazil

Background: Telomeres are protein complexes located at the top of each arm of chromosomes, essential for maintaining the stability of the genome. Telomere shortening is found in physiological aging and senescence-related to systemic lupus erythematosus (SLE). Objectives: To compare the relative telomere length (TL) in patients with SLE and controls and to correlate the TL with clinical characteristics, treatments, disease activity, and damage. Methods: A cross-sectional study comparing SLE patients and controls, from 18 to 60 years old, matched by sex and age. Clinical and demographic data from all participants were collected, and relative TL by qPCR. For cases, previous and current history, disease activity, damage, cognitive assessment, fatigue, presence of depression, anxiety, stress symptoms, and physical activity were analyzed. Results were obtained using frequencies and percentages for qualitative characteristics and measures of central tendency and standard deviation for quantitative ones. Comparisons of relative TL and other variables were performed using the t-Student test when assumptions of normality and homoscedasticity were satisfied and the Mann-Whitney test otherwise. A significance level of 5% was considered. Results: Sixty SLE patients and 55 controls were included. Among patients, 75% were diagnosed in adulthood; 86.7% were female (mean age 37 years); 15% had antiphospholipid syndrome (APS), 51.7% had a previous history of nephritis, and 23.3% had neuropsychiatric involvement. Among controls, 87.3% were female (mean age 38 years). There was no difference between groups regarding sex and age (p=0.924 and p=0.737, respectively). SLE patients had a median relative TL of 0.80 versus 1.07 in the control group (p=0.005). In the multiple regression model (R 2 =18.4%), patients with anxiety symptoms in a moderate grade had lower TL (p=0.015) when compared to patients without or with low-grade anxiety symptoms. In contrast, patients with APS had longer telo

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Genetic drivers of heterogeneity in type 2 diabetes pathophysiology

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Nature 2024年第8003期627卷 347-357页

作者： Ken Suzuki Konstantinos Hatzikotoulas Lorraine Southam Henry J Taylor Xianyong Yin Kim M Lorenz Ravi Mandla Alicia Huerta-Chagoya Giorgio E M Melloni Stavroula Kanoni Nigel W Rayner Ozvan Bocher Ana Luiza Arruda Kyuto Sonehara Shinichi Namba Simon S K Lee Michael H Preuss Lauren E Petty Philip Schroeder Brett Vanderwerff Mart Kals Fiona Bragg Kuang Lin Xiuqing Guo Weihua Zhang Jie Yao Young Jin Kim Mariaelisa Graff Fumihiko Takeuchi Jana Nano Amel Lamri Masahiro Nakatochi Sanghoon Moon Robert A Scott James P Cook Jung-Jin Lee Ian Pan Daniel Taliun Esteban J Parra Jin-Fang Chai Lawrence F Bielak Yasuharu Tabara Yang Hai Gudmar Thorleifsson Niels Grarup Tamar Sofer Matthias Wuttke Chloé Sarnowski Christian Gieger Darryl Nousome Stella Trompet Soo-Heon Kwak Jirong Long Meng Sun Lin Tong Wei-Min Chen Suraj S Nongmaithem Raymond Noordam Victor J Y Lim Claudia H T Tam Yoonjung Yoonie Joo Chien-Hsiun Chen Laura M Raffield Bram Peter Prins Aude Nicolas Lisa R Yanek Guanjie Chen Jennifer A Brody Edmond Kabagambe Ping An Anny H Xiang Hyeok Sun Choi Brian E Cade Jingyi Tan K Alaine Broadaway Alice Williamson Zoha Kamali Jinrui Cui Manonanthini Thangam Linda S Adair Adebowale Adeyemo Carlos A Aguilar-Salinas Tarunveer S Ahluwalia Sonia S Anand Alain Bertoni Jette Bork-Jensen Ivan Brandslund Thomas A Buchanan Charles F Burant Adam S Butterworth Mickaël Canouil Juliana C N Chan Li-Ching Chang Miao-Li Chee Ji Chen Shyh-Huei Chen Yuan-Tsong Chen Zhengming Chen Lee-Ming Chuang Mary Cushman John Danesh Swapan K Das H Janaka de Silva George Dedoussis Latchezar Dimitrov Ayo P Doumatey Shufa Du Qing Duan Kai-Uwe Eckardt Leslie S Emery Daniel S Evans Michele K Evans Krista Fischer James S Floyd Ian Ford Oscar H Franco Timothy M Frayling Barry I Freedman Pauline Genter Hertzel C Gerstein Vilmantas Giedraitis Clicerio González-Villalpando Maria Elena González-Villalpando Penny Gordon-Larsen Myron Gross Lindsay A Guare Sophie Hackinger Liisa Hakaste Sohee Han Andrew T Hattersley Christian Herder Momoko Horikoshi Annie-Green Howard Willa Centre for Genetics and Genomics Versus Arthritis Centre for Musculoskeletal Research Division of Musculoskeletal and Dermatological Sciences University of Manchester Manchester UK. Department of Diabetes and Metabolic Diseases Graduate School of Medicine University of Tokyo Tokyo Japan. Department of Statistical Genetics Osaka University Graduate School of Medicine Suita Japan. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. konstantinos.hatzikotoulas@helmholtz-munich.de. Institute of Translational Genomics Helmholtz Zentrum München German Research Center for Environmental Health Neuherberg Germany. Center for Precision Health Research National Human Genome Research Institute National Institutes of Health Bethesda MD USA. British Heart Foundation Cardiovascular Epidemiology Unit Department of Public Health and Primary Care University of Cambridge Cambridge UK. Heart and Lung Research Institute University of Cambridge Cambridge UK. Department of Epidemiology School of Public Health Nanjing Medical University Nanjing China. Department of Biostatistics and Center for Statistical Genetics University of Michigan Ann Arbor MI USA. Corporal Michael J. Crescenz VA Medical Center Philadelphia PA USA. Department of Systems Pharmacology and Translational Therapeutics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Department of Genetics University of Pennsylvania Perelman School of Medicine Philadelphia PA USA. Programs in Metabolism and Medical and Population Genetics Broad Institute of Harvard and MIT Cambridge MA USA. Diabetes Unit and Center for Genomic Medicine Massachusetts General Hospital Boston MA USA. TIMI Study Group Division of Cardiovascular Medicine Brigham and Women's Hospital Harvard Medical School Boston MA USA. William Harvey Research Institute Barts and the London School of Medicine and Dentistry Queen Mary University of London L

Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.

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Improvement of extracellular polysaccharides production from Cordyceps militaris immobilized alginate beads in repeated-batch fermentation

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LWT 2024年 193卷

作者： Hou, Shi-Jing Cheng, Kuan-Chen Lin, Shyh-Hsiang Hsiao, I-Lun Santoso, Shella Permatasari Singajaya, Stephanie Chou, Yu-Chieh Lin, Shin-Ping Master Program in Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Institute of Biotechnology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei10617 Taiwan Graduate Institute of Food Science and Technology National Taiwan University 1 Roosevelt Rd. Sec. 4 Taipei10617 Taiwan Department of Medical Research China Medical University Hospital China Medical University 91 Hsueh-Shih Rd. Taichung40402 Taiwan Department of Optometry Asia University 500 Lioufeng Rd. Wufeng Taichung41354 Taiwan School of Nutrition and Health Sciences Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan School of Food Safety Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Department of Chemical Engineering Widya Mandala Surabaya Catholic University Kalijudan 37 East Java Surabaya60114 Indonesia Collaborative Research Center for Sustainable and Zero Waste Industries Kalijudan 37 East Java Surabaya60114 Indonesia Ph.D. Program in Drug Discovery and Development Industry Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan Research Center of Biomedical Device Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan TMU Research Center for Digestive Medicine Taipei Medical University 250 Wu-Hsing Street Taipei11031 Taiwan

Cordyceps militaris (C. militaris) is a unique medicinal fungus of the genus Cordyceps. It has high economic value due to various biological functions from the extracellular polysaccharides (EPSs) it produces. The aim of this study was to establish a mycelium-immobilization system for EPS production in a bubble column system. First, EPS production was optimized by 90.2% (from 0.72 to 1.37 g/L) using response surface methodology under an alginate-immobilized mycelium system with 6 days of cultivation. The highest EPS production was obtained (5.3 g/L) in a flask system through elongation to 15 days of cultivation. EPS production subsequently further increased to 10.42 g/L utilizing a bubble column reactor. Furthermore, the system can be reused for at least three rounds. In the EPS characteristics analysis, the produced EPSs were mainly composed of glucose and galactose. They presented strong antibacterial activity against Staphylococcus aureus. In terms of antioxidant activity, respective the EPS concentration that caused 50% scavenging of DPPH and ABTS free radicals values (IC50) were 4.65 and 7.92 mg/mL. In summary, these findings should be helpful for establishing a suitable industrial fermentation system for C. militaris and can be studied in the food and medical industries in future work. © 2024 The Authors

关键词： Mycelium

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Chronic exposure to glyphosate induces cardiac remodeling without functional damage and promotes hepatic morphological and biochemical alterations in rats

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Life sciences 2025年 377卷 123801页

作者： Raissa de Oliveira Mantovani Gabriela Vidotto Cavallieri Gomes Eduardo Daniel da Silva Larissa Ferreira Ros Mariano Allice Santos Cruz Veras Giovana Rampazzo Teixeira Giovanna Fachetti Frigoli Glaura Scantamburlo Alves Fernades Rejane Batista Brinholi Victorino da Silva Renata Calciolari Rossi Francis Lopes Pacagnelli Postgraduate Program in Animal Science University of Western São Paulo (UNOESTE) Presidente Prudente São Paulo Brazil. University of Western São Paulo (UNOESTE) Presidente Prudente São Paulo Brazil. Department of Physical Education São Paulo State University (UNESP) School of Technology and Sciences Presidente Prudente SP Brazil Multicenter Graduate Program in Physiological Sciences SBFis São Paulo State University (UNESP) Presidente Prudente SP Brazil. Department of General Biology Biological Sciences Center State University of Londrina - UEL Brazil. Postgraduate Program in Animal Science University of Western São Paulo (UNOESTE) Presidente Prudente São Paulo Brazil Faculty of Health Sciences Physiotherapy Program UNOESTE Presidente Prudente Brazil. Electronic address: francispacagnelli@unoeste.br.

AIM:This study aimed to evaluate the effects of chronic inhalation of different glyphosate concentrations on cardiac and hepatic structure and function in rats. METHODS:Forty-two male Wistar rats were randomly divided into three groups control (C, n = 14), exposed to 10 mL of distilled water; low concentration (LC, n = 14), exposed to 3.71 × 10 g of active ingredient per hectare (g.a.i./ha); and high concentration (HC, n = 14), exposed to 9.28 × 10 g.a.i./ha. Exposure occurred via inhalation for 180 days. After the exposure period, echocardiography was performed to assess cardiac function, followed by euthanasia and the collection of heart and liver tissues. Cardiac tissue was subjected to histological analysis, assessment of oxidative stress, inflammation and apoptosis markers, collagen quantification, and fractal dimension analysis. In the liver, histopathological evaluation, fractal dimension analysis, and serum biochemical measurements of ALT and AST were performed. KEY FINDINGS:No cardiac functional impairment was observed. Similarly, anatomical and histomorphometrical assessments showed no structural modifications, and the BAX/BCL-2 ratio remained unchanged. However, the HC group showed increased myocardial collagen, elevated CAT activity, and reduced GST and TNF-α, indicating remodeling with an adaptive antioxidant response. In the liver, the HC group presented histological changes compatible with fibrosis, increased ALT, and decreased AST levels, suggesting hepatic damage, although fractal dimension analysis revealed no significant architectural disruption. SIGNIFICANCE:Chronic inhalation exposure to glyphosate resulted in cardiac remodeling characterized by increased collagen deposition and an adaptive antioxidant response, without functional impairment. In the liver, it led to fibrosis and enzymatic alterations, despite preserved microarchitectural organization.

关键词： Fibrosis Glyphosate Heart Liver Remodeling cardiac

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