Pub Date : 2024-11-26DOI: 10.1038/s41684-024-01486-0
Jorge Ferreira
{"title":"Sex differences in response to stress and alcohol abuse","authors":"Jorge Ferreira","doi":"10.1038/s41684-024-01486-0","DOIUrl":"10.1038/s41684-024-01486-0","url":null,"abstract":"","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"358-358"},"PeriodicalIF":5.9,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01486-0.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142714737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-25DOI: 10.1038/s41684-024-01473-5
Cedric Moro, Christophe Magnan
Preclinical mouse models are extensively used in biomedical research to gain insight into disease mechanisms and to test new drug treatments. Glucose and insulin tolerance tests are simple experimental tests frequently used worldwide to assess glucose metabolism in mice. Various guidelines and methodological considerations have been published to help researchers standardize procedures and optimize research outcomes. Yet, there is still important experimental heterogeneity in the way these simple procedures are performed, with no real consensus on what the best practices are to achieve high-quality research and reproducible results. Here we critically examine several published guidelines and recent technical reports on how to perform these metabolic tests in laboratory mice and discuss the influence of various confounding factors on test results. We hope this work will help scientists establish more consensual guidelines for maximizing the relevance and clinical translation of studies using mouse models in metabolic research. In this Review, the authors examine current guidelines for metabolic tolerance tests in mice and provide a set of revisited recommendations to improve the reproducibility and clinical translation of the findings.
{"title":"Revisited guidelines for metabolic tolerance tests in mice","authors":"Cedric Moro, Christophe Magnan","doi":"10.1038/s41684-024-01473-5","DOIUrl":"10.1038/s41684-024-01473-5","url":null,"abstract":"Preclinical mouse models are extensively used in biomedical research to gain insight into disease mechanisms and to test new drug treatments. Glucose and insulin tolerance tests are simple experimental tests frequently used worldwide to assess glucose metabolism in mice. Various guidelines and methodological considerations have been published to help researchers standardize procedures and optimize research outcomes. Yet, there is still important experimental heterogeneity in the way these simple procedures are performed, with no real consensus on what the best practices are to achieve high-quality research and reproducible results. Here we critically examine several published guidelines and recent technical reports on how to perform these metabolic tests in laboratory mice and discuss the influence of various confounding factors on test results. We hope this work will help scientists establish more consensual guidelines for maximizing the relevance and clinical translation of studies using mouse models in metabolic research. In this Review, the authors examine current guidelines for metabolic tolerance tests in mice and provide a set of revisited recommendations to improve the reproducibility and clinical translation of the findings.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"54 1","pages":"16-23"},"PeriodicalIF":5.9,"publicationDate":"2024-11-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01473-5.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142697096","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-22DOI: 10.1038/s41684-024-01459-3
Lauren A. Burgett, Theres B. Alexander, Haley A. Moya, Marcy A. Kingsbury
The translational value of the marble burying task (MBT) is debatable. Here we performed video analysis of behaviors during the MBT to accurately capture the details of all behaviors displayed during this task. Our results show that a count of marbles buried at the end of the task may not be a good translational correlate of the ‘intentional marble burying’ that the task is assumed to measure. Rather, the number of marbles buried may be measuring accidental marble burying due to ‘rapid digging’. Video analysis during MBT provides a novel approach to characterize the many behaviors displayed during this task and may explain inconsistencies reported in the literature. However, the number of marbles buried at the end of the MBT may still have value as a screening test for anxiogenic or anxiolytic interventions. Any interventions that show significant alterations in the number of marbles buried can be pursued further through more robust and comprehensive behavior scoring methods. The marble burying task (MBT) is used to measure anxiety-like behavior, relying on a snapshot of the number of marbles buried at the end of the test. This Brief Communication introduces a more extensive behavioral analysis to improve the translational value of MBT for clinical psychological phenotypes.
{"title":"A revision to marble burying: video analysis during the marble burying task is imperative to understanding rodent behavior","authors":"Lauren A. Burgett, Theres B. Alexander, Haley A. Moya, Marcy A. Kingsbury","doi":"10.1038/s41684-024-01459-3","DOIUrl":"10.1038/s41684-024-01459-3","url":null,"abstract":"The translational value of the marble burying task (MBT) is debatable. Here we performed video analysis of behaviors during the MBT to accurately capture the details of all behaviors displayed during this task. Our results show that a count of marbles buried at the end of the task may not be a good translational correlate of the ‘intentional marble burying’ that the task is assumed to measure. Rather, the number of marbles buried may be measuring accidental marble burying due to ‘rapid digging’. Video analysis during MBT provides a novel approach to characterize the many behaviors displayed during this task and may explain inconsistencies reported in the literature. However, the number of marbles buried at the end of the MBT may still have value as a screening test for anxiogenic or anxiolytic interventions. Any interventions that show significant alterations in the number of marbles buried can be pursued further through more robust and comprehensive behavior scoring methods. The marble burying task (MBT) is used to measure anxiety-like behavior, relying on a snapshot of the number of marbles buried at the end of the test. This Brief Communication introduces a more extensive behavioral analysis to improve the translational value of MBT for clinical psychological phenotypes.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"387-389"},"PeriodicalIF":5.9,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142684290","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1038/s41684-024-01472-6
Maria Victoria Gómez-Gaviro, Vicente Llorente
Optical tissue clearing allows high-resolution microscopy imaging of biological samples while retaining critical three-dimensional and structural information for research and diagnosis. Most methods can only be performed ex vivo on fixed tissues, but a new study claims to have found a technique that can render live tissue transparent.
{"title":"In vivo optical tissue clearing using light-absorbing dyes","authors":"Maria Victoria Gómez-Gaviro, Vicente Llorente","doi":"10.1038/s41684-024-01472-6","DOIUrl":"10.1038/s41684-024-01472-6","url":null,"abstract":"Optical tissue clearing allows high-resolution microscopy imaging of biological samples while retaining critical three-dimensional and structural information for research and diagnosis. Most methods can only be performed ex vivo on fixed tissues, but a new study claims to have found a technique that can render live tissue transparent.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"361-362"},"PeriodicalIF":5.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637549","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1038/s41684-024-01476-2
Jan Lauwereyns, Jeffrey Bajramovic, Bettina Bert, Samuel Camenzind, Joery De Kock, Alisa Elezović, Sevilay Erden, Fernando Gonzalez-Uarquin, Yesim Isil Ulman, Orsolya Ivett Hoffmann, Maria Kitsara, Nikolaos Kostomitsopoulos, Winfried Neuhaus, Benoit Petit-Demouliere, Simone Pollo, Brígida Riso, Sophie Schober, Athanassia Sotiropoulos, Aurélie Thomas, Augusto Vitale, Doris Wilflingseder, Arti Ahluwalia
Many scientific breakthroughs have depended on animal research, yet the ethical concerns surrounding the use of animals in experimentation have long prompted discussions about humane treatment and responsible scientific practice. First articulated by Russell and Burch, the 3Rs Principles of Replacement, Reduction, and Refinement have gained widespread recognition as basic guidelines for animal research. Over time, the 3Rs have transcended the research community, influencing policy decisions, animal welfare advocacy and public perception of animal experimentation. Despite their broad acceptance, interpretations of the 3Rs vary substantially, shaping statutory frameworks at various levels, with both technical and practical impacts.
{"title":"Toward a common interpretation of the 3Rs principles in animal research","authors":"Jan Lauwereyns, Jeffrey Bajramovic, Bettina Bert, Samuel Camenzind, Joery De Kock, Alisa Elezović, Sevilay Erden, Fernando Gonzalez-Uarquin, Yesim Isil Ulman, Orsolya Ivett Hoffmann, Maria Kitsara, Nikolaos Kostomitsopoulos, Winfried Neuhaus, Benoit Petit-Demouliere, Simone Pollo, Brígida Riso, Sophie Schober, Athanassia Sotiropoulos, Aurélie Thomas, Augusto Vitale, Doris Wilflingseder, Arti Ahluwalia","doi":"10.1038/s41684-024-01476-2","DOIUrl":"10.1038/s41684-024-01476-2","url":null,"abstract":"Many scientific breakthroughs have depended on animal research, yet the ethical concerns surrounding the use of animals in experimentation have long prompted discussions about humane treatment and responsible scientific practice. First articulated by Russell and Burch, the 3Rs Principles of Replacement, Reduction, and Refinement have gained widespread recognition as basic guidelines for animal research. Over time, the 3Rs have transcended the research community, influencing policy decisions, animal welfare advocacy and public perception of animal experimentation. Despite their broad acceptance, interpretations of the 3Rs vary substantially, shaping statutory frameworks at various levels, with both technical and practical impacts.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"347-350"},"PeriodicalIF":5.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01476-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637550","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-15DOI: 10.1038/s41684-024-01460-w
Andy J. Chua, Valentina Di Francesco, Anisha D’Souza, Mansoor Amiji, Benjamin S. Bleier
The blood–brain barrier (BBB) poses a substantial obstacle to the successful delivery of therapeutics to the central nervous system (CNS). The transnasal route has been extensively explored, but success rates have been modest due to challenges related to the precise anatomical placement of drugs, the small volumes that the olfactory cleft can accommodate and short drug residence times due to mucociliary clearance. Here, to address these issues, we have developed a surgical technique known as the minimally invasive nasal depot (MIND), which allows the accurate placement of depot drugs into the submucosal space of the olfactory epithelium of rats. This technique exploits the unique anatomy of the olfactory apparatus to enable transnasal delivery of drugs into the CNS, bypassing the BBB. In our rat model, a bony window is created in the animal snout to expose the submucosal space. Using the MIND technique, we have successfully delivered oligonucleotides to the CNS in Sprague-Dawley and Long-Evans rats, leading to an upregulation of brain-derived neurotrophic factor in the substantia nigra and hippocampus. In this Protocol, we describe the procedural steps for MIND. This procedure takes about 45 min and can be performed by researchers with basic surgical skills. We additionally describe modifications to perform MIND in mice, which are anatomically smaller. The MIND procedure represents a unique platform that can be used to overcome the limitations posed by the BBB. This technique can potentially expand the therapeutic toolkit in the treatment of neurological diseases. This Protocol describes a minimally invasive technique for central nervous system drug delivery in rodents. The procedure allows the use of the transnasal route to deliver blood–brain barrier-impermeant drugs.
血脑屏障（BBB）是将治疗药物成功输送到中枢神经系统（CNS）的一大障碍。人们对经鼻途径进行了广泛探索，但成功率不高，原因在于药物的精确解剖位置、嗅裂所能容纳的体积小以及粘膜清除导致的药物停留时间短等挑战。为了解决这些问题，我们开发了一种称为微创鼻腔药库（MIND）的手术技术，可以将药库药物准确地放置到大鼠嗅上皮的粘膜下空间。这项技术利用嗅觉器官的独特解剖结构，绕过生物BB，经鼻将药物输送到中枢神经系统。在我们的大鼠模型中，我们在动物鼻腔开了一个骨窗，以暴露粘膜下空间。利用 MIND 技术，我们成功地将寡核苷酸输送到 Sprague-Dawley 大鼠和 Long-Evans 大鼠的中枢神经系统，导致黑质和海马中的脑源性神经营养因子上调。在本《规程》中，我们将介绍 MIND 的程序步骤。该过程耗时约 45 分钟，具备基本手术技能的研究人员即可完成。我们还介绍了在解剖学上更小的小鼠中进行 MIND 的修改。MIND 程序是一个独特的平台，可用于克服 BBB 带来的限制。这项技术有可能扩展治疗神经系统疾病的工具包。
{"title":"Murine model of minimally invasive nasal depot (MIND) technique for central nervous system delivery of blood–brain barrier-impermeant therapeutics","authors":"Andy J. Chua, Valentina Di Francesco, Anisha D’Souza, Mansoor Amiji, Benjamin S. Bleier","doi":"10.1038/s41684-024-01460-w","DOIUrl":"10.1038/s41684-024-01460-w","url":null,"abstract":"The blood–brain barrier (BBB) poses a substantial obstacle to the successful delivery of therapeutics to the central nervous system (CNS). The transnasal route has been extensively explored, but success rates have been modest due to challenges related to the precise anatomical placement of drugs, the small volumes that the olfactory cleft can accommodate and short drug residence times due to mucociliary clearance. Here, to address these issues, we have developed a surgical technique known as the minimally invasive nasal depot (MIND), which allows the accurate placement of depot drugs into the submucosal space of the olfactory epithelium of rats. This technique exploits the unique anatomy of the olfactory apparatus to enable transnasal delivery of drugs into the CNS, bypassing the BBB. In our rat model, a bony window is created in the animal snout to expose the submucosal space. Using the MIND technique, we have successfully delivered oligonucleotides to the CNS in Sprague-Dawley and Long-Evans rats, leading to an upregulation of brain-derived neurotrophic factor in the substantia nigra and hippocampus. In this Protocol, we describe the procedural steps for MIND. This procedure takes about 45 min and can be performed by researchers with basic surgical skills. We additionally describe modifications to perform MIND in mice, which are anatomically smaller. The MIND procedure represents a unique platform that can be used to overcome the limitations posed by the BBB. This technique can potentially expand the therapeutic toolkit in the treatment of neurological diseases. This Protocol describes a minimally invasive technique for central nervous system drug delivery in rodents. The procedure allows the use of the transnasal route to deliver blood–brain barrier-impermeant drugs.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"363-375"},"PeriodicalIF":5.9,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142637551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1038/s41684-024-01475-3
Shuai Qiu, Jingyan Jia, Benlei Xu, Nan Wu, Huaqiang Cao, Shuangyi Xie, Jialong Cui, Ji Ma, Yi-Hsuan Pan, Xiao-Bing Yuan
Developing cost-effective and disease-relevant animal models is essential for advancing biomedical research into human disorders. Here we investigate the feasibility of a pig model for autism spectrum disorder (ASD) using embryonic exposure to valproic acid (VPA), an antiepileptic drug known to increase ASD risk. We established experimental paradigms to assess the behavioral characteristics of these pig models. Administration of VPA to Bama miniature pigs (Sus scrofa domestica) during critical embryonic stages resulted in abnormal gait, increased anxiety levels, reduced learning capabilities and altered social patterns, while largely preserving social preference of treated piglets. Notably, we detected significant neuroanatomical changes in cortical regions associated with ASD in the VPA-treated pigs, including cortical malformation, increased neuronal soma size, decreased dendritic complexity and reduced dendritic spine maturation. Transcriptome analysis of the prefrontal cortex of VPA-treated pigs further revealed substantial alterations in the expression of genes linked to ASD, especially genes of the dopamine signaling pathway, highlighting the model’s relevance and potential for shedding light on ASD’s underlying neuropathological and molecular mechanisms. These findings suggest that pig models could serve as a promising alternative to traditional rodent models and provide a more ethical substitute for the use of primates in translational research on neurodevelopmental disorders. This study describes a new pig model of autism induced by embryonic exposure to valproic acid. The pig model displays behavioral alterations, abnormal gait and increased anxiety, which recapitulate key features of autism.
{"title":"Development and evaluation of an autism pig model","authors":"Shuai Qiu, Jingyan Jia, Benlei Xu, Nan Wu, Huaqiang Cao, Shuangyi Xie, Jialong Cui, Ji Ma, Yi-Hsuan Pan, Xiao-Bing Yuan","doi":"10.1038/s41684-024-01475-3","DOIUrl":"10.1038/s41684-024-01475-3","url":null,"abstract":"Developing cost-effective and disease-relevant animal models is essential for advancing biomedical research into human disorders. Here we investigate the feasibility of a pig model for autism spectrum disorder (ASD) using embryonic exposure to valproic acid (VPA), an antiepileptic drug known to increase ASD risk. We established experimental paradigms to assess the behavioral characteristics of these pig models. Administration of VPA to Bama miniature pigs (Sus scrofa domestica) during critical embryonic stages resulted in abnormal gait, increased anxiety levels, reduced learning capabilities and altered social patterns, while largely preserving social preference of treated piglets. Notably, we detected significant neuroanatomical changes in cortical regions associated with ASD in the VPA-treated pigs, including cortical malformation, increased neuronal soma size, decreased dendritic complexity and reduced dendritic spine maturation. Transcriptome analysis of the prefrontal cortex of VPA-treated pigs further revealed substantial alterations in the expression of genes linked to ASD, especially genes of the dopamine signaling pathway, highlighting the model’s relevance and potential for shedding light on ASD’s underlying neuropathological and molecular mechanisms. These findings suggest that pig models could serve as a promising alternative to traditional rodent models and provide a more ethical substitute for the use of primates in translational research on neurodevelopmental disorders. This study describes a new pig model of autism induced by embryonic exposure to valproic acid. The pig model displays behavioral alterations, abnormal gait and increased anxiety, which recapitulate key features of autism.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"376-386"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01475-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599535","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-11-12DOI: 10.1038/s41684-024-01474-4
Natascha Drude, Stefan Nagel-Riedasch, Stephan P. Rosshart, Andreas Diefenbach, The “Charité 3R Wildling Mouse Model in Health and Disease (C3R Wildling HeaD)” consortium, Stefan Jordan
Mice with a natural microbiome are a promising research model for basic and applied science because of their closer resemblance to the human superorganism compared to mice born and raised under stringent hygiene conditions. Consequently, biomedical therapies developed and tested in “Wildling mice” hold great potential for successful translation into clinical applications. Over the past four years, scientists, veterinarians and institutional officials at Charité – Universitätsmedizin Berlin, supported by the University Hospital Erlangen, have designed a facility for Wildling mice and developed a conceptual framework for safe and ethical preclinical research involving mice with a natural microbiome.
{"title":"A facility for laboratory mice with a natural microbiome at Charité – Universitätsmedizin Berlin","authors":"Natascha Drude, Stefan Nagel-Riedasch, Stephan P. Rosshart, Andreas Diefenbach, The “Charité 3R Wildling Mouse Model in Health and Disease (C3R Wildling HeaD)” consortium, Stefan Jordan","doi":"10.1038/s41684-024-01474-4","DOIUrl":"10.1038/s41684-024-01474-4","url":null,"abstract":"Mice with a natural microbiome are a promising research model for basic and applied science because of their closer resemblance to the human superorganism compared to mice born and raised under stringent hygiene conditions. Consequently, biomedical therapies developed and tested in “Wildling mice” hold great potential for successful translation into clinical applications. Over the past four years, scientists, veterinarians and institutional officials at Charité – Universitätsmedizin Berlin, supported by the University Hospital Erlangen, have designed a facility for Wildling mice and developed a conceptual framework for safe and ethical preclinical research involving mice with a natural microbiome.","PeriodicalId":17936,"journal":{"name":"Lab Animal","volume":"53 12","pages":"351-354"},"PeriodicalIF":5.9,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.com/articles/s41684-024-01474-4.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142599532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"农林科学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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