Browsing by Subject "mice"

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  • Åhlgren, Johanna; Voikar, Vootele (2019)
    Individually ventilated caging (IVC) systems for rodents are increasingly common in laboratory animal facilities. However, the impact of such substantial change in housing conditions on animal physiology and behavior is still debated. Most importantly, there arise the questions regarding reproducibility and comparison of previous or new phenotypes between the IVC and open cages. The present study was set up for detailed and systematic comparison of behavioral phenotypes in male and female mice of three widely used inbred strains (C57BL/6JRccHsd, DBA/2JRccHsd, 129S2/SvHSd) after being kept in two housing environments (IVC and open cages) for 6?weeks (since 4?weeks of age) before behavioral testing. The tests addressed exploratory, anxiety-like and stress-related behavior (light-dark box, open field, forced swim test, stress-induced hyperthermia), social approach and species-specific behavior (nest building, marble burying). In all tests, large and expected strain differences were found. Somewhat surprisingly, the most striking effect of environment was found for basal body temperature and weight loss after one night of single housing in respective cages. In addition, the performance in light-dark box and open field was affected by environment. Several parameters in different tests showed significant interaction between housing and genetic background. In summary, the IVC housing did not invalidate the well-known differences between the mouse strains which have been established by previous studies. However, within the strains the results can be influenced by sex and housing system depending on the behavioral tasks applied. The bottom-line is that the environmental conditions should be described explicitly in all publications.
  • Depommier, Clara; Van Hul, Matthias; Everard, Amandine; Delzenne, Nathalie M.; De Vos, Willem M.; Cani, Patrice D. (2020)
    Accumulating evidence points to Akkermansia muciniphila as a novel candidate to prevent or treat obesity-related metabolic disorders. We recently observed, in mice and in humans, that pasteurization of A. muciniphila increases its beneficial effects on metabolism. However, it is currently unknown if the observed beneficial effects on body weight and fat mass gain are due to specific changes in energy expenditure. Therefore, we investigated the effects of pasteurized A. muciniphila on whole-body energy metabolism during high-fat diet feeding by using metabolic chambers. We confirmed that daily oral administration of pasteurized A. muciniphila alleviated diet-induced obesity and decreased food energy efficiency. We found that this effect was associated with an increase in energy expenditure and spontaneous physical activity. Strikingly, we discovered that energy expenditure was enhanced independently from changes in markers of thermogenesis or beiging of the white adipose tissue. However, we found in brown and white adipose tissues that perilipin2, a factor associated with lipid droplet and known to be altered in obesity, was decreased in expression by pasteurized A. muciniphila. Finally, we observed that treatment with pasteurized A. muciniphila increased energy excretion in the feces. Interestingly, we demonstrated that this effect was not due to the modulation of intestinal lipid absorption or chylomicron synthesis but likely involved a reduction of carbohydrates absorption and enhanced intestinal epithelial turnover. In conclusion, this study further dissects the mechanisms by which pasteurized A. muciniphila reduces body weight and fat mass gain. These data also further support the impact of targeting the gut microbiota by using specific bacteria to control whole-body energy metabolism.
  • Törnävä, Marja (Helsingfors universitet, 2012)
    Literature review: Cognitive deficits of schizophrenia include disturbances in executive functions, working memory, attention and information processing. Improved understanding of the neurobiology of these deficits depends on the availability of reliable and carefully validated animal models, which can assist the development of novel pharmacotherapies. The glutamate hypothesis of schizophrenia arises from observations that substances which block a type of glutamate receptor known as N-methyl-D-aspartate-receptor (NMDAR) induces schizophrenia-like condition. The evidence strongly supports the use of NMDAR antagonists to model schizophrenia in animals. In this literature review various cognitive animal models of schizophrenia are presented. Also heterogeneity in the effects of NMDAR antagonists, at the cognitive level, following single-dose or long-term exposure is reviewed and discussed. Experimental part: Attentional set shifting task (ASST) is a cognitive animal model, which models animal's cognitive flexibility or ability to shift attentional set. The ASST has been modified for use with mice. Validation of the test in mice is still inadequate. The main purpose of this study was to investigate whether ASST is suitable for an outbred ICR mouse strain. The current study failed to demonstrate the suitability of ICR mice in this test. Though results did prove that ICR mice are capable of performing the technical requirements of the test. The pharmacological focus of this study was to investigate in mice how a subchronically administrated NMDAR antagonist dizocilpine (MK-801) (0.03-0.1 mg/kg, 10-14 d, i.p.) influences the ability to shift attentional set. With our experimental design we could not measure the ability to shift attentional set thus we cannot conclude whether or not MK-801 influenced this cognitive domain. Results did reveal that MK-801, as administrated above, did not alter the motivation or motor functions in ICR mice. According to literature and this current study it is obvious that more research is needed to clear ASST suitability for mice. Future studies should focus to investigate how the components of the experimental arrangement in ASST affect the test performance.
  • Voikar, Vootele; Gaburro, Stefano (2020)
    Animal models of neurodegenerative and neuropsychiatric disorders require extensive behavioral phenotyping. Currently, this presents several caveats and the most important are: (i) rodents are nocturnal animals, but mostly tested during the light period; (ii) the conventional behavioral experiments take into consideration only a snapshot of a rich behavioral repertoire; and (iii) environmental factors, as well as experimenter influence, are often underestimated. Consequently, serious concerns have been expressed regarding the reproducibility of research findings on the one hand, and appropriate welfare of the animals (based on the principle of 3Rs—reduce, refine and replace) on the other hand. To address these problems and improve behavioral phenotyping in general, several solutions have been proposed and developed. Undisturbed, 24/7 home-cage monitoring (HCM) is gaining increased attention and popularity as demonstrating the potential to substitute or complement the conventional phenotyping methods by providing valuable data for identifying the behavioral patterns that may have been missed otherwise. In this review, we will briefly describe the different technologies used for HCM systems. Thereafter, based on our experience, we will focus on two systems, IntelliCage (NewBehavior AG and TSE-systems) and Digital Ventilated Cage (DVC®, Tecniplast)—how they have been developed and applied during recent years. Additionally, we will touch upon the importance of the environmental/experimenter artifacts and propose alternative suggestions for performing phenotyping experiments based on the published evidence. We will discuss how the integration of telemetry systems for deriving certain physiological parameters can help to complement the description of the animal model to offer better translation to human studies. Ultimately, we will discuss how such HCM data can be statistically interpreted and analyzed.