10 research outputs found

    A systematic review of the development and application of home cage monitoring in laboratory mice and rats

    Get PDF
    Funding Information: Open Access funding enabled and organized by Projekt DEAL. VV is supported by Jane and Aatos Erkko Foundation. Funding Information: The Vienna BioCenter Core Facilities (VBCF) Preclinical Phenotyping Facility acknowledges funding from the Austrian Federal Ministry of Education, Science & Research; and the City of Vienna. Funding Information: This article is based upon work from COST Action “Improving biomedical research by automated behaviour monitoring in the animal home-cage” (TEATIME; CA20135; cost-teatime.org) supported by COST (European Cooperation in Science and Technology). Funding Information: PK, PM, AJ, BL, CTR, LL, and KH were funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy—EXC 2002/1 “Science of Intelligence” —project number 390523135. Funding Information: This article is based upon work from COST Action “Improving biomedical research by automated behaviour monitoring in the animal home-cage” (TEATIME; CA20135; cost-teatime.org) supported by COST (European Cooperation in Science and Technology). Publisher Copyright: © 2023, The Author(s).Background: Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Results: Both the absolute (~ × 26) and relative (~ × 7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011–2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systems; intermediate time periods (4–12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviors; the main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently. Conclusions: Over the period covered in this study, techniques for HCM of mice and rats have improved considerably. This development is ongoing and further progress as well as validation of HCM systems will extend the applications to allow for continuous, longitudinal, non-invasive monitoring of an increasing range of parameters in group-housed small rodents in their home cages.publishersversionpublishe

    Focus on novel approaches: Home-cage monitoring of laboratory mice

    Get PDF
    Assessment of behavioural phenotype is crucial for the evaluation of various disease models, particularly inlaboratory rodents. Traditionally, this includes performing a variety of conventional tests where animals areremoved from their home-cages and placed in behavioural test apparatuses. This approach can be affected bymicro-environmental stress (removal from cage, handling, moving to an unfamiliar setting, and the test itself)and other biases by capturing animals’ responses in a short time-window and potentially missing subtle or circadianeffects. Overall, serious concerns have been expressed regarding the validity and reliability of such measurements.To address some of these concerns, researchers are increasingly resorting to automated home-cage monitoring(HCM) technologies, which allow continuous recording of behavioural and physiological parameters ofundisturbed animals. In 2021, a pan-European network of researchers started the 4-year COST Action “Improvingbiomedical research by automated behaviour monitoring in the animal home-cage” (CA20135 TEATIME,https://www.cost-teatime.org/). For this project, experts from different fields joined forces to critically assess thepotential of available technologies, to develop guidelines and identify where further technological development isneeded, including analysis of big data. The opportunities opened by HCM for daily health and welfare monitoringof laboratory mice in a contactless, stress-free, and continuous fashion are also being explored. We providea short overview of the progress made by the Action during the first year and a half (presentation available athttps://osf.io/5dgz7)

    Focus on novel approaches: Home-cage monitoring of laboratory mice

    No full text
    Assessment of behavioural phenotype is crucial for the evaluation of various disease models, particularly in laboratory rodents. Traditionally, this includes performing a variety of conventional tests where animals are removed from their home-cages and placed in behavioural test apparatuses. This approach can be affected by micro-environmental stress (removal from cage, handling, moving to an unfamiliar setting, and the test itself) and other biases, by capturing animals’ responses in a short time-window and potentially missing subtle or circadian effects. Overall, serious concerns have been expressed regarding the validity and reliability of such measurements. To address some of these concerns, researchers are increasingly resorting to automated home-cage monitoring (HCM) technologies, which allow recording behavioural and physiological parameters of undisturbed animals continuously. In 2021, a pan-European network of researchers started the 4-year COST Action “Improving biomedical research by automated behaviour monitoring in the animal home-cage” (CA20135 TEATIME, https://www.cost-teatime.org/), where experts from different fields joined forces to critically assess the potential of available technologies, to develop guidelines and identify where further technological development is needed, including analysis of big data. The opportunities opened by home-cage monitoring for daily health and welfare monitoring of laboratory mice in a contactless, stress-free, and continuous fashion are also being duly explored. We provide a short overview of the progress made by the Action during the first year and a half (presentation available at https://osf.io/5dgz7)

    A systematic review of the development and application of home cage monitoring in laboratory mice and rats

    Full text link
    Background Traditionally, in biomedical animal research, laboratory rodents are individually examined in test apparatuses outside of their home cages at selected time points. However, the outcome of such tests can be influenced by various factors and valuable information may be missed when the animals are only monitored for short periods. These issues can be overcome by longitudinally monitoring mice and rats in their home cages. To shed light on the development of home cage monitoring (HCM) and the current state-of-the-art, a systematic review was carried out on 521 publications retrieved through PubMed and Web of Science. Results Both the absolute (~×26) and relative (~×7) number of HCM-related publications increased from 1974 to 2020. There was a clear bias towards males and individually housed animals, but during the past decade (2011–2020), an increasing number of studies used both sexes and group housing. In most studies, animals were kept for short (up to 4 weeks) time periods in the HCM systemsintermediate time periods (4–12 weeks) increased in frequency in the years between 2011 and 2020. Before the 2000s, HCM techniques were predominantly applied for less than 12 h, while 24-h measurements have been more frequent since the 2000s. The systematic review demonstrated that manual monitoring is decreasing in relation to automatic techniques but still relevant. Until (and including) the 1990s, most techniques were applied manually but have been progressively replaced by automation since the 2000s. Independent of the year of publication, the main behavioral parameters measured were locomotor activity, feeding, and social behaviorsthe main physiological parameters were heart rate and electrocardiography. External appearance-related parameters were rarely examined in the home cages. Due to technological progress and application of artificial intelligence, more refined and detailed behavioral parameters have been investigated in the home cage more recently

    Heme oxygenase-1 inhibits myoblast differentiation by targeting myomirs

    No full text
    AIMS: Heme oxygenase-1 (HMOX1) is a cytoprotective enzyme degrading heme to biliverdin, iron ions, and carbon monoxide, whose expression is induced in response to oxidative stress. Its overexpression has been suggested as a strategy improving survival of transplanted muscle precursors. Results: Here we demonstrated that HMOX1 inhibits differentiation of myoblasts and modulates miRNA processing: downregulates Lin28 and DGCR8, lowers the total pool of cellular miRNAs, and specifically blocks induction of myomirs. Genetic or pharmacological activation of HMOX1 in C2C12 cells reduces the abundance of miR-1, miR-133a, miR-133b, and miR-206, which is accompanied by augmented production of SDF-1 and miR-146a, decreased expression of MyoD, myogenin, and myosin, and disturbed formation of myotubes. Similar relationships between HMOX1 and myomirs were demonstrated in murine primary satellite cells isolated from skeletal muscles of HMOX1(+/+), HMOX1(+/−), and HMOX1(−/−) mice or in human rhabdomyosarcoma cell lines. Inhibition of myogenic development is independent of antioxidative properties of HMOX1. Instead it is mediated by CO-dependent inhibition of c/EBPδ binding to myoD promoter, can be imitated by SDF-1, and partially reversed by enforced expression of miR-133b and miR-206. Control C2C12 myoblasts injected to gastrocnemius muscles of NOD-SCID mice contribute to formation of muscle fibers. In contrast, HMOX1 overexpressing C2C12 myoblasts form fast growing, hyperplastic tumors, infiltrating the surrounding tissues, and disseminating to the lungs. Innovation: We evidenced for the first time that HMOX1 inhibits differentiation of myoblasts, affects the miRNA processing enzymes, and modulates the miRNA transcriptome. Conclusion: HMOX1 improves the survival of myoblasts, but concurrently through regulation of myomirs, may act similarly to oncogenes, increasing the risk of hyperplastic growth of myogenic precursors. Antioxid. Redox Signal. 16, 113–127

    Development and application of home cage monitoring in laboratory mice and rats: a systematic review

    No full text
    We are conducting a systematic review on home cage monitoring in laboratory mice and rats. A major advantage of home cage monitoring is that the animals can be examined in their home environment, which reduces stress and allows to monitor the animals 24/7. Moreover, this approach minimizes the influence of the human presence on the animals’ behavior. Therefore, home cage-based monitoring is interesting for phenotyping in mice and rats since it may reduce data variability and improve reproducibility. In addition, it can provide a useful tool for welfare assessment. The requirements for home cage monitoring changed over the last decades driven by technology and digitalization. The goal of this systematic review is to identify these historical changes and describe the current state of the art. After phase 1 (title/Abstract screening), it was decided to perform phase 2 (full text screening) and phase 3 (data extraction) simultaneously. Therefore, an updated protocol was uploaded

    PPAR\gamma activation but not PPAR\gamma haplodeficiency affects proangiogenic potential of endothelial cells and bone marrow-derived progenitors

    Get PDF
    Background. Peroxisome proliferator-activated receptor-? (PPAR?) agonists, which have been used as insulin sensitizers in diabetic patients, may improve functions of endothelial cells (ECs). We investigated the effect of PPAR? on angiogenic activities of murine ECs and bone marrow-derived proangiogenic cells (PACs). Methods. PACs were isolated from bone marrow of 10¿12 weeks old, wild type, db/db and PPAR? heterozygous animals. Cells were cultured on fibronectin and gelatin coated dishes in EGM-2MV medium. For in vitro stimulations, rosiglitazone (10 ?mol/L) or GW9662 (10 ?mol/L) were added to 80% confluent cell cultures for 24 hours. Angiogenic potential of PACs and ECs was tested in vitro and in vivo in wound healing assay and hind limb ischemia model. Results. ECs and PACs isolated from diabetic db/db mice displayed a reduced angiogenic potential in ex vivo and in vitro assays, the effect partially rescued by incubation of cells with rosiglitazone (PPAR? activator). Correction of diabetes by administration of rosiglitazone in vivo did not improve angiogenic potential of isolated PACs or ECs. In a hind limb ischemia model we demonstrated that local injection of conditioned media harvested from wild type PACs improved the blood flow restoration in db/db mice, confirming the importance of paracrine action of the bone marrow-derived cells. Transcriptome analysis showed an upregulation of prooxidative and proinflammatory pathways, and downregulation of several proangiogenic genes in db/db PACs. Interestingly, db/db PACs had also a decreased level of PPAR? and changed expression of PPAR?-regulated genes. Using normoglycemic PPAR?+/? mice we demonstrated that reduced expression of PPAR? does not influence neovascularization either in wound healing or in hind limb ischemia models. Conclusions. In summary, activation of PPAR? by rosiglitazone improves angiogenic potential of diabetic ECs and PACs, but decreased expression of PPAR? in diabetes does not impair angiogenesis
    corecore